Breast Cancer Survivors

Chemo Secrets From a Breast Cancer Survivor

Undergoing chemotherapy can be one of the most terrifying things that you go through in your life. One of the most frightening things about chemotherapy is the lack of real information that most people have about it, and the unknown makes it so much more frightening as a result. This eBook, written by a young cancer survivor gives you the real story about what chemo is all about. The most valuable information you can get about chemotherapy is from someone that has already experienced it. This PDF eBook allows you to download and read it as soon as your order it. You can begin your journey of reassurance as soon as you want! Because that's what this is about: chemo does not have to be a terrifying unknown! Other people have gone through it before, and want to help you through it as well! This eBook is the guide through chemo that many people wish they could have had, and now you can have it yourself! Read more here...

Chemo Secrets From a Breast Cancer Survivor Overview

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Assessment Of Breast Cancerprone Families

Building the case for hereditary cancer is frequently based upon the cardinal clinical features of hereditary cancer (namely, early age of cancer onset, pattern of multiple primary cancers such as breast and ovarian cancer , vertical transmission of cancer, and increased number of cancer occurrences) (Table 1-1). It is virtually axiomatic that the larger the breast cancer-prone family, the greater the number of expected carcinomas of the breast or ovary. One can be more confident of a likely hereditary etiology for breast cancer if there is evidence for earlier age of onset of cancer, especially when there is familial clustering of these cancers, particularly ovarian cancer, among primary and secondary relatives (see Table 1-1). In such a setting, there is an increased probability that a germ-line mutation (BRCA1, BRCA2) will be found. On the other hand, when dealing with families that are small, there may be a limited number of patients with cancer, a deficit of

Heterogeneity And Hereditary Breast Cancer

Virtually all forms of hereditary cancer show significant genetic and phenotypic heterogeneity. For example, breast cancer occurs in significant excess in disorders associated with extra-breast cancer sites, such as Li-Fraumeni syndrome (Figure 1-1), Bloom's syndrome, Cowden's disease, ataxia-telangiectasia, the breast-gastrointestinal tract cancer syndrome, extraordinarily early-onset breast cancer (Figure 1-2), and the HBOC syndrome (Figure 1-3). Undoubtedly, other tumor combinations and or hereditary syndromes which will qualify as hereditary breast cancer are yet to be identified. Space does not allow a discussion of each of these breast cancer-associated disorders (for more detail see Lynch and colleagues18). Clearly, it is no longer appropriate to characterize hereditary breast cancer as a generic term. Rather, one must be more precise and denote the particular breast cancer-associated Breast cancer at < 30 years of age Breast cancer at < 40 years of age Breast cancer at...

Examples Two Prognostic Studies in Breast Cancer

We consider the data of two studies of patients with node-positive breast cancer. The first, a clinical trial GBSG-2 study, n 686 patients, 299 events for event-free survival (EFS) is used to identify prognostic markers and to investigate the influence of different model-building strategies. This dataset was used previously for prognostic modelling for example, by Sauerbrei and Royston (1999) and Schumacher et al. (2006) and is available at The data of the second, smaller Freiburg-DNA study (n 139 patients, 76 events for EFS) are exclusively used to validate the results obtained in the GBSG-2 study. Prognostic markers evaluated in both studies were patient's age, menopausal status, tumour

Conservative Versus Conventional Surgery In Hereditary Breast Cancer

Should a patient with HBOC, particularly one who is harboring a BRCA1 or BRCA2 germline mutation, be managed differently from a patient with the more common sporadic form of this disease We have taken the position that, because of the early age of breast cancer onset and excess lifetime risk for bilaterality, coupled with the potential deficiency of repair of radiation-induced DNA damage,44 the patient should be given the option of total mastectomy as opposed to conservative (lumpec-tomy) management, and seriously consider contralateral prophylactic mastectomy, assuming that the ipsilateral breast cancer is likely to have adequate control.

Surveillance And Management For Hereditary Breast Cancer

When the diagnosis of a hereditary breast cancer-prone syndrome has been established, the surveillance and management strategies are then melded to the natural history of the particular HBC syndrome. We recommend that patients receive intensive education regarding the natural history, genetic risk, and availability of DNA testing such as BRCA1, BRCA2, or p53, depending upon the hereditary breast cancer syndrome of concern. We initiate such education between the ages of 15 and 18 years but do not perform any DNA testing until the patient is > 18 years of age and has given informed consent.

Breast Cancer Risk and Management Chemoprevention Surgery and Surveillance

In the past decade, the systematic use of mammography as part of diagnostic screening programs and the extensive use of stereotactic fine-needle biopsy techniques have greatly improved our ability to detect pre-invasive as well as microinvasive breast carcinomas. The consequent earlier detection of breast lesions is considered the most important factor explaining the recent decline in overall mortality from breast cancer observed in the United States.1 This progress has translated into many efforts to gain insight into the biologic mechanisms responsible for cancer development and progression and to identify potential areas of intervention for prevention studies.2 About 20 percent of women diagnosed with proliferative breast disease display atypical hyperplasia, a condition associated with increased risk of breast cancer and probably a precursor to the disease.3 The recognition of the importance of these benign breast lesions as risk factors and the identification of genetic...

Breast Cancer Risk Assessment

Chemoprevention is traditionally defined as the inhibition or reversal of carcinogenesis, before overt malignancy, by intervention with chemical agents. Most breast cancer chemopreventive studies are conducted within cohorts of women considered at high risk of the disease.7 In the context of chemoprevention investigations, the most important cancer risk factors are considered to be those that can be measured quantitatively in the subject at risk. These factors are called risk biomarkers, and they can be used to identify cohorts for chemoprevention trials.8 Generally, the risk biomarkers are grouped in the following categories (1) genetic predisposition, (2) carcinogen exposure, (3) carcinogen effect exposure, (4) previous cancers, and (5) intermediate biomarkers. In some cases, risk biomarkers that are measurable and may undergo selective modulation by chemopreven-tive agents can be used as SEBs in clinical chemoprevention studies.9 Today, there is not a single ideal risk biomarker or...

Breast Cancer in Women on Estrogen Replacement Therapy

Bergkvist and co-workers25 compared 261 women who developed breast cancer while on ERT to 6,617 breast cancer patients who had no recorded treatment with estrogen. The relative survival rate over an 8-year period was higher in the breast cancer patients who had previously received ERT. This corresponded to a 32 percent reduction in excess mortality. Gambrell,26 in a prospective study, also evaluated the effect on survival in breast cancer patients diagnosed while on ERT. Mortality was 22 percent among those diagnosed with breast cancer while on ERT compared to 46 percent among those who had never received hormone replacement. Henderson and colleagues27 observed a 19 percent reduction in breast cancer mortality among 4,988 previous ERT users, compared to 3,865 nonusers who subsequently developed this disease.

Exposure To Exogenous Or Endogenous Estrogen During Breast Cancer Development

The decision whether or not to take hormone replacement remains difficult for the post-menopausal woman because of conflicting risks and benefits and is even more difficult for the breast cancer survivor for whom there is even less data. One can therefore analyze situations in which women are inadvertently exposed to exogenous or endogenous estrogen at a time when they may have been harboring subclinical breast cancer. Does such exposure adversely affect survival outcome for these patients Such situations include those in which the diagnosis of breast cancer is made in postmenopausal women receiving ERT at the time of diagnosis or in whom the diagnosis is made in pregnancy or during lactation, or in those women with a history of oral contraceptive pill use around the time of diagnosis of breast cancer.

Breast Cancer Associated with Pregnancy

Pregnancy coincident with, or subsequent to, the detection of breast cancer provides another excellent opportunity to evaluate the outcome of breast cancer patients inadvertently exposed to high levels of estrogen at times when they were harboring occult disease. During pregnancy, the serum levels of estriol increase 50-fold. Only 0.5 to 4 percent of all breast cancers are diagnosed during pregnancy. Because the average breast cancer remains occult in the breast some 5 to 8 years prior to diagnosis, some authors include in this category women in whom a diagnosis of breast cancer has been made within 12 months of delivery. The outcome in women with subclinical breast cancers exposed to elevated levels of progesterone and estrogen under these circumstances could provide insight into the influence of these hormones on the malignant disease process. The physiologic changes and engorgement that occur in the breast during pregnancy often hinder early detection of breast cancer. This results...

Evaluation and Surgical Management of Stage I and II Breast Cancer

Implementation of screening mammography and increased breast cancer awareness account for the vast majority of breast cancers presenting at an earlier stage. This combined with extensive data supporting the choice of breast preservation has lead to a dramatic change in the treatment for early stage breast cancer. Halsted firmly established radical mastectomy as the sole surgical procedure for breast cancer. Although this provided improved locoregional control of disease, the results were disfiguring (Figure 9-1, right breast). Clinical trials have led to the evolution of therapy that has lessened physical deformity (Figure 9-1, Figure 9-2) and improved survival.

Studies On Estrogenreplacement Therapy In Breast Cancer Survivors

DiSaia36 reported on 71 breast cancer survivors who received ERT. There was no exclusion based on time interval from diagnosis, stage, age, receptor status, or lymph node status. Women received combination therapy with progestin only if they had not previously undergone hysterectomy. Later, the author reported a comparison of 41 of these ERT survivors to 82 non-ERT breast cancer subjects, matched for both age and stage of disease.37 Survival analysis did not indicate a significant difference between the two groups. An updated series of 145 patients who received ERT for at least 3 months after diagnosis has identified 13 recurrences. The duration of estrogen use prior to the diagnosis of recurrent breast cancer ranged from 4 months to 11.5 years (Figures 15-1 and 15-2). Other authors have reported their experience of ERT in breast cancer survivors. Eden38 reported six recurrences among 90 women receiving ERT. These ERT users were matched two to one with control subjects with no history...

Estrogen Replacement Therapy for Breast Cancer Survivors

Given the current population, 30 million women in the United States will spend approximately 40 percent of their lifetime in the post-menopausal period. These women have a lifetime risk of one in eight of developing breast cancer. Thus, a considerable number of American women are likely to have a history of breast cancer treatment and at the same time be potential candidates for hormone-replacement therapy. In the last decade, indications for chemotherapy as adjuvant treatment to surgery have widened and now encompass many more premenopausal women.1 Adjuvant therapy for breast cancer includes the use of alkylating The major concern of many physicians in prescribing estrogen-replacement therapy (ERT) for breast cancer survivors is the theory that metastatic quiescent tumor foci might be activated and the fire of breast cancer ignited by the fuel estrogen. Other fears are that estrogen might cause a second primary in the already environmentally genetically primed contralateral breast or...

Breast Cancer in Oral Contraceptive Pill Users

Given the long natural history of this neoplasm, it is certain that a large number of patients subsequently diagnosed with breast cancer have used oral contraceptive pills (OCP) during the genesis and progression of their malignant disease process they are another group that deserves examination. Rosner33 evaluated 347 women < 50 diagnosed with breast cancer, of whom 112 were OCP users. The distribution of tumor size, estrogen-receptor status, and family and reproductive history was the same between the two cohorts. There was no difference in disease-free survival or survival between the two groups. Women who used OCP within a year of diagnosis of their breast cancer had a similar survival to those who had discontinued use > 1 year before. There was no difference in survival among those who used OCP > 10 years prior to their diagnosis of breast cancer. Schonborn and colleagues34 evaluated the influence of a positive history of OCP use on survival. Four hundred and seventy-one...

Breast Cancer Chemopreventive Agents

The importance of estrogens as breast cancer promoters has been sustained by direct and indirect observations since the 1960s. An important source of indirect evidence is provided by the relevant clinical observations derived from clinical trials of the adjuvant use of tamoxifen. Several large randomized studies have demonstrated that adjuvant therapy with the nonsteroidal antiestrogen tamoxifen citrate is associated with reduction in the risk of developing a second contralateral primary breast cancer by 30 to 50 percent.88-90

Treatment of Metastatic Breast Cancer

Despite the improvements in prognosis achieved for many patients with breast cancer, approximately 46,000 women die of this disease each year. The increase in incidence of breast cancer seen through the early 1990s has been successfully offset by two factors widespread application of screening mammography, permitting more frequent early diagnosis and, more recently, the decrease in recurrence and mortality rates achieved through the now standard application of effective systemic adjuvant therapy.1 Unfortunately, similar gains have not been achieved for women who present with metastatic breast cancer or for those with distant disease relapse after initial treatment. For these women, palliation of symptoms and some prolongation of survival is possible but there is no known curative treatment. In fact, the death rate for this disease has remained stubbornly constant over decades.2 Metastatic breast cancer is the second most common cause of cancer death among women. While only 6 percent...

Breast Cancer and Radiation Therapy

The role of radiation therapy in the treatment of breast cancer has been affected by shifting trends in treatment. Historically, mastectomy was the surgical treatment of choice for all stages of disease. In later times, radiation therapy was found to significantly reduce the risk of local recurrence. Pioneers in radiotherapy such as Gilbert Fletcher published important dose response data for the control of regional adenopathy.1 As the treatment of breast cancer has changed, the role of radiotherapy has evolved for all stages of disease. Breast conservation therapy for ductal carcinoma in situ (intraductal) and early-stage invasive cancer has been shown to provide equivalent survival to mastectomy in properly selected patients. The importance of cosmesis in breast conserving treatment can not be underestimated. Issues of self-esteem and sensuality add complexity to the treatment decision. Breast conservation therapy (BCT) is clearly established as a standard treatment for early-stage...

Comparative Pathology of Breast Cancer

The initial studies of mouse mammary tumors questioned whether the mouse tumors were related in any way to human breast cancer. Livingood states that he undertook his studies in 1894 at the suggestion of Dr. Welsh, of Johns Hopkins fame, who told him that comparative pathology was a worthy pursuit (Livingood, 1896). In 1911, Bashford provided an extensive rationale for studying mouse mammary tumor biology (Bashford, 1911b). In 1945, Shimkin further defended the focus of NCI on mouse mammary tumorigenesis (Shimkin, 1945). As recorded herein, each development in either clinical breast cancer or in basic breast cancer research has led to research in the other field. The MMTV-induced tumors have always been recognized as being morphologically distinct from human breast cancers. Some authorities have speculated that the differences are due to the supposed large ductal origin of human breast cancer as compared to the acinar origin of mouse mammary tumors (Dunn, 1945, 1958). However, the...

Evaluation Of Various Tests Used In Breast Cancer

The American Society of Clinical Oncology (ASCO) established an expert panel to evaluate the use of various tests in breast cancer.5 The panel modified the scale developed by the Canadian Taskforce on Periodic Health Examination to evaluate various tests (Table 16-1).6 There are only two prospective randomized trials that have evaluated the impact of a multitude of surveillance tests on the overall survival and quality of life in breast cancer patients. They fulfill the criteria of providing Level 1, that is, highest level of evidence. However, beginning with studies published in 1979 by Winchester and colleagues,7 a large database has been developed that has retrospectively analyzed the value of various diagnostic tests in the follow-up of breast cancer patients. These studies have tried to answer some of the following questions 1. Do the available tests diagnose early asymptomatic recurrence in breast cancer If so, which tests are useful Winchester and colleagues analyzed 87...

Surveillance of the Breast Cancer Patient

In recent years, extensive clinical trials have established the roles for conservative surgery, radiation, and adjuvant chemo hormonal therapy in the primary therapy of breast cancer. It may seem self-evident that repeated postoperative contact between cancer patients and their physicians, that is, follow-up, is a good thing. Follow-up practice patterns vary greatly, with some oncologists frequently following their breast cancer patients with various intensive investigation and others only doing sporadic follow-up. The possible beneficial effects of follow-up include

Locally Advanced Breast Cancer

Integration of systemic chemotherapy and or hormonal therapy with surgery and irradiation is considered the standard of care in the treatment of locally advanced breast cancer (LABC). Because the greatest risk for patients with LABC is the development of distant metastases and subsequent death, the goals of surgery are to provide maximal locoregional control with minimal disfigurement and to permit accurate staging to determine prognosis. Breast conservation surgery is sometimes possible after tumor downstaging with induction chemotherapy, but close cooperation between the medical and surgical oncologists and the radiation therapist is required to determine the feasibility of this option. Similarly, the surgeon must be familiar with the natural history of LABC to assess the advisability of major resections of either persistent advanced primary disease or locoregional recurrences. If life expectancy is very short, as is the case with patients who have bulky visceral disease or...

Adjuvant Systemic Therapy of Early Breast Cancer

The modern era of breast cancer treatment began over 100 years ago with the development of surgical techniques that emphasized the need for total resection of tumor. Nevertheless, despite gross total excision, many patients with seemingly localized disease suffered relapse or distant recurrence and died of their cancer. This was presumably due to the growth of microscopic tumor unappreciated at the time of initial therapy. The need for additional, adjuvant therapy after surgery led to numerous randomized controlled trials (RCTs) addressing the problem. The role of adjuvant systemic therapy in increasing survival and decreasing mortality has been established by these studies and confirmed by overview meta-analyses. The basis for this success is the recognition of and adherence to the principles of adjuvant therapy, which are that (1) local treatments do not cure all patients with seemingly localized cancer (2) populations at high risk of relapse can be identified (3) patterns of...

Definition Of Locally Advanced Breast Cancer

Locally advanced breast cancer generally refers to large primary tumors (> 5 cm) associated with skin or chest-wall involvement or with fixed (matted) axillary lymph nodes (T3 T4 N2 N3).1 In the most recent TNM staging system,1 tumors associated with disease in the ipsi-lateral supraclavicular nodal basin have been eliminated from the LABC category because the supraclavicular basin lies outside the primary lymphatic drainage pathways of the axilla and internal mammary nodes tumors associated with supraclavicular disease have been reclassified as stage IV disease. However, as patients with distant metastases confined to supraclavicular nodes have a better prognosis than patients with metastases at other distant sites and can be rendered disease free with locoregional therapy,2 metastases limited to the ipsilateral sub- or supraclavicular fossa will be included in the definition of LABC offered here. Large primary tumors (> 5 cm) with no evidence of nodal involvement (T3 N0) have a...

Radiotherapy For Locally Advanced Breast Cancer

Early studies of local-regional radiotherapy following mastectomy for locally advanced disease showed reduced recurrences in the axilla, supraclavicular fossa, and chest wall. However, these patients experienced an increase in non-breast cancer-related mortality that negated the Cardiac toxicity due to chest wall radiotherapy is purported to be the causative factor in the increase in nonbreast cancer-related mortality. Concerns about cardiac morbidity from radiotherapy in the face of potentially cardiotoxic adriamycin-based chemotherapy led to decreased use of postmastectomy radiotherapy. Technical factors in historically quoted studies may explain the high incidence of radiation cardiac When patients treated with orthovoltage radiotherapy were excluded from analysis, a survival benefit of approximately 10 percent was seen in the patients receiving chest wall radio-therapy.104 Recently, two prospective randomized studies reported results showing survival advantage from the addition of...

Inflammatory Breast Cancer

Because today's combination chemotherapy regimens can often render inflammatory breast cancer (IBC) resectable, mastectomy now has a role in the treatment of this disease. In our review of 178 women treated for IBC in dox-orubicin-based multimodality therapy protocols between 1974 and 1993, the addition of mastectomy led to significant improvement in locoregional disease control.36 Locoregional relapse rates were 16.3 percent (16 of 98 patients) for patients who underwent chemotherapy, mastectomy, and radiotherapy, and 35.7 percent (15 of 42 patients) for patients who underwent only chemotherapy and radiotherapy (p .016). However, when patients were stratified on the basis of tumor response to induction chemotherapy, only patients with a partial response to chemotherapy demonstrated significant improvement in local control with the addition of mastectomy. As only 12 percent of patients (21 of 178) had a complete clinical response, demonstration of a statistically significant...

Chemotherapy Table 138

In AIDS-related PCNSL, there is no optimum regimen of chemotherapy. In the largest combined chemotherapy and radiation regimen trial, a single cycle of CHOD followed by RT, the median survival rate of 2.4 months was similar to that of radiation therapy alone.39 Chamberlain and colleagues40 studied whole-brain radiation therapy plus hydroxyurea radiosensitization, followed by procarbazine lomustine vincristine (PCV), and while the study did show a longer than average survival, approximately 13 months, the individuals represented a highly selected population of patients, all that had a much higher pretreatment functional status in regards to their disease.

Chemotherapy Without HAART in the HAART

Chemotherapy without antiretrovirals has been studied due to concerns of drug interactions with chemotherapy and noncompliance with HAART resulting in increased resistance.81 Further, protease inhibitors (in HAART regimens) have been associated with neutropenia with concomitant chemotherapy.98 The National Cancer Institute used a dose-adjusted regimen of etoposide, vincristine, and doxorubicin (4 days), and daily oral prednisone (5 days), followed by cyclophosphamide. The study consisted of 39 patients and antiretrovirals were not given until after the final cycle of chemotherapy. A CR rate of 74 was achieved.99

Preoperative Chemotherapy

Another approach of recent interest and active study but not yet standard of care is chemotherapy alone followed by surgery. Two large, published, randomized trials provide conflicting results. The US study led by Kelsen and colleagues (1998) evaluated three cycles of 5-fluorouracil (5-FU) and cisplatin followed by surgery and found no difference in survival. The UK Medical Research Council study led by McDonald evaluated two cycles of 5-FU and cisplatin followed by surgery and found a survival benefit to preoperative chemotherapy. Given the difficulty in resolving these opposing results, further trials are awaited, and preoperative chemotherapy alone should be used only in the setting of a clinical trial.

Is there an Adverse Interaction between Interstitial Brachytherapy and Chemotherapy

The first evidence presented in this regard was reported by Kuske et al. (2002) from the RTOG 95-17 trial. In their study, grade 3 toxicity was significantly increased with the use of chemotherapy. This was true for both HDR and LDR techniques, but particularly so for LDR implants. Similarly, Arthur et al. (2003) found that APBI with an LDR interstitial technique was associated with a significant decrement in cosmetic outcome when patients also received Adriamycin-based chemotherapy. In the combined Tufts Brown VCU series (Wazer et al. 2006) of HDR interstitial brachy-therapy, the use of Adriamycin-based chemotherapy was associated with an increased risk of clinically evident fat necrosis, grade 1 2 skin toxicity, and suboptimal cosmetic scores. In contrast, no adverse interactive effect has yet been found between the use of chemotherapy and the MammoSite catheter (Vicini et al. 2005).

Chemotherapy and Radiation Therapy

Chemotherapy and radiation therapy are important instruments in the palliation of incurable rectal cancer and are generally indicated in patients with unresectable local disease that present with nerve pain, ureteral obstruction, and extensive pelvic sidewall involvement with compression of Tumors that are asymptomatic or minimally symptomatic are at low risk of obstruction and can be treated with chemotherapy or combination chemoradiation therapy. In lesions that are obstructing or near obstructing, mechanical palliation is required in the form of surgery or endorectal stenting before the initiation of chemotherapy. However, although formerly many experts advised that every patient with a large resectable rectal cancer should be operated on, almost irrespective of the extent of metastatic disease to prevent obstruction, this recommendation had to be modified in more recent years. As a rule, tumors that are unlikely to obstruct in an 8 to 10-week period will not require palliative...

Multimodality Therapy For Locally Advanced Breast Cancer

Neoadjuvant chemotherapy is the subject of intense clinical investigation for tumor down-staging before surgery. Patients who otherwise would not be candidates for breast conservation therapy may experience a significant reduction in tumor burden after neoadjuvant therapy allowing for local excision with negative margins. Response rates are reported to be approximately 65 to 75 percent.114-116 Studies have shown no detriment to overall survival when compared to standard postoperative treatment. Complete clinical response may define a more favorable subgroup than a partial response although this has not been universally noted.117 What is the optimal therapy for women experiencing a complete response In one study, those patients who had a complete clinical response to chemotherapy who then received radiotherapy to the breast without surgery had a higher local recurrence rate than those with partial response, local excision, and subsequent radiotherapy.118 Residual disease, although not...

Chemotherapy and Radiation

Currently, there is much debate about whether chemotherapy and or radiotherapy should replace surgical resection as the primary treatment modality in tumors that do not respond to antibiotic therapy (Bozzetti et al, 1993). Surgical advocates argue that resection is vital for accurate staging and histological classification, and that having an entire specimen allows the pathologist to adequately evaluate the specimen. With the advances in obtaining biopsies endo-scopically and in immunohistopathology, however, these arguments for surgery are becoming less powerful. The main arguments against nonsurgical treatment is that chemotherapy and radiotherapy can lead to necrosis of the tumor, resulting in gastric perforation or bleeding. Late complications of radiotherapy, particularly involving the abdominal and retroperitoneal viscera, are also concerns that must be considered. These complications include visceral and ureteric stricture, cystitis, enteritis, anal sphincter dysfunction, and...

Polyneuropathy and chemotherapy

Toxic neuropathies caused by chemotherapy are usually dose-dependent, and have a potential reversibility after termination of the drug treatment. Little is known about the influence of preexisting polyneuropathies in the development of a chemotherapeutically induced neuropathy (except vincristine given in patients with hereditary sensorimotor neuropathy), and the toxicity of only a few drug combinations have been described. This is of importance as chemotherapy is not always used as a single agent therapy, but patients often receive drug combinations or second line therapy. Additionally also biological agents such as antibodies, interferons, cytokines and vaccines are used in cancer therapy and also have a risk of inducing polyneuropathies.

Systemic Chemotherapy

Systemic chemotherapy for HCC has historically resulted in very low response rates and no improvement in the 5-year survival rate of approximately 5 . Response rates of only 0 to 20 have been reported with treatment of unresectable HCC with cytotoxic agents such as 5-fluorouracil, paclitaxel, doxorubicin, cisplatin, vinblastine, etoposide, and mitoxantrone, as single agents or in combinations. Given the modest response rates to traditional chemotherapy, new innovative regimens that target molecular abnormalities are warranted. At M. D. Anderson Cancer Center, we have been interested in strategies aimed at inhibiting the epidermal growth factor (EGF) receptor, which has been shown to induce mitogenic activity in vivo in numerous cell types, including hepatocytes. OSI-774 (Tarceva) is an orally active, potent, selective inhibitor of the EGF receptor tyrosine kinase that blocks cell-cycle progression in the Gi phase. OSI-774 is currently being studied in both a phase II clinical trial in...

Combination Therapy Metronomic Chemotherapy

The production of pro- and antiapoptotic molecules changes during the course of conventional therapy for cancer. Specifically, prior studies show that surgery and chemotherapy, in contrast to irradiation, may even enhance tumor angiogenesis by stimulating production of VEGF and other endothelial cell survival and growth factors in tumor cells.339 High local VEGF concentrations in the BM microenvironment of MM patients suppress the antiproliferative effects of several chemotherapeutics, thereby promoting multidrug resistance.340'341 Therefore, combining chemotherapies and irradiation with drugs that block VEGF signaling may enhance antitumor efficacy, for example, by normalizing tumor vasculature and thereby improving oxygenation and delivery of chemotherapies to tumor cells.342 Enhanced antitumor activity of conventional chemotherapy343-345 and irradiation346,347 regimens has been achieved when combined with antiangiogenic drugs. Novel therapeutic strategies of metronomic...

Chemotherapy and Steroids

In HIV-infected individuals, several chemotherapy regimens have been tried, but generally low-dose alkylating agents have been used.246 In a pre-HAART study by Oksenhendler et al.,237 1 2 of 20 patients were treated with chemotherapy. Of the 12 patients, nine received vinblastine with resulting partial response with loss of constitutional symptoms and regression of lymphadenopathy. Four of them remained stable, but required maintenance therapy every 2 weeks, and five of these individuals relapsed and required combination chemotherapy or splenectomy. In another study, two HIV-infected individuals not on HAART and with aggressive MCD were treated with oral etoposide. Remission, documented by computerized tomography (CT) was achieved at a follow-up of 1.5 and 6 months, with minimal side effects. It was concluded by Scott et al.247 in this study that oral etoposide may be a safe, tolerable, and active agent in MCD. In a retrospective study by Loi and colleagues,242 11 patients, ten of...

Regional Chemotherapy

The rationale for regional chemotherapy by hepatic arterial infusion (HAI) is based upon the recognition that the liver is the most likely site of distant metastases for CRC and it has a unique dual blood supply, with the hepatic vein serving as the primary source of vascularization for the normal parenchyma while the hepatic artery supplies tumor. Fluorodeoxyuridine (FUDR) is the preferred agent for HAI delivery. When delivered by HAI, > 90 of FUDR is extracted by the liver on first pass with an estimated 100-to 400-fold increase in hepatic exposure when compared to intravenous administration (Ensminger, 2002). A metaanalysis including 654 patients with unresectable hepatic metastases enrolled in 7 randomized trials comparing HAI to systemic 5-FU therapy did show greater tumor response rates with HAI (41 vs 14 ,p < .001). However there was no significant survival advantage (16 months vs 12.2 months, p .14) (Meta-Analysis Group in Cancer, 1996). Kerr and colleagues (2003)...

Adjuvant Chemotherapy for CRC

Although surgery remains the primary curative modality for localized disease, the presence of micrometastases will be responsible for disease relapse in a significant proportion of patients. Six months of5-FU LV remains the current standard of care for adjuvant therapy following resection of high risk localized CRC, credited with a one-third decrease in the risk of disease recurrence and death (Macdonald and Astrow, 2001). For patients with node-positive colon cancer, this translates into an overall absolute 5-year survival improvement from approximately 50 to 60 to 65 , as was observed in Intergroup 0035, the first trial to confirm the efficacy of adjuvant therapy (Table 97-3). In the subsequent Intergroup 0089 randomized trial of 3759 patients with resected high risk stage II (node-negative) or stage III (node-positive) colon cancer, no advantage was observed with 12 months of therapy over 6 months, or with the addition of levamisole (an antihelminthic biomodulator of 5-FU) to LV....

Selective Hepatic Intraarterial Chemotherapy

Hepatic Artery Infusion Pump

Liver specific adjuvant chemotherapy following resection of colorectal metastases Use in hepatocellular carcinoma and other metastatic carcinomas can be considered under certain circumstances A right subcostal approach is used. The falciform ligament is divided and the porta hepatis is exposed further by gentle superior retraction of the liver. Cholecystectomy is performed to eliminate the postoperative complication of chemical cholecystitis induced by infusional chemotherapy. The gastrohepatic ligament is divided with care to avoid injury to a replaced left hepatic artery (if present). All duodenal and antral vessels must be ligated to eliminate the possibility of reflux of chemotherapy into these regions as this may lead to chemical duodenitis or gastritis. The common hepatic, gastroduodenal, and proper hepatic arteries are identified by dissection of the hepatoduodenal ligament and marked with vessel loops.

Usefulness of Mammography for Breast Cancer Screening

An essential component in determining the efficacy of a screening program is an evaluation of benefits versus risk of harm. For mammography, the major risks to be addressed include radiation-induced breast cancer and the effects of false-positive and false-negative diagnoses. The balancing of potential benefit and harm has been, and continues to be, difficult because of the limited amount of available data. However, it is possible to estimate the recall rate and biopsy-requested rate of mammography screening and to estimate the breast cancer mortality reduction from screening. It is also possible to estimate the average radiation dose received per examination, and the level of risk of radiation-induced breast cancer. When these are considered in the context of the natural incidence of carcinoma of the breast, a benefit risk ratio can be

Mammographic Appearance Of Breast Cancer

Breast cancer has numerous clinical and imaging presentations. The classic mammographic appearance of infiltrating breast cancer is an irregular mass, often with ill-defined or spiculated margins. In addition to a discrete mass, the invasive tumor can also present as a subtle asymmetric density or an architectural distortion. Clustered pleomorphic calcifications are the common presentation of in situ carcinoma that may or may not be associated with invasive disease. Secondary signs of malignancy, often associated with advanced stages of breast cancer, are detectable clinically and radiographically as areas of skin thickening or dimpling, nipple retraction, and axillary adenopathy. Diffuse skin thickening and breast edema manifested as increased mammographic density are associated with lymphangitic spread of cancer involving the dermal lymphatics with inflammatory cancer. The underlying primary tumor is often obscured by the diffuse breast edema. These findings must be differentiated...

Imaging Specific Types of Infiltrating Breast Cancer

Approximately 85 percent of breast carcinomas arise from ductal structures, with the remaining 15 percent arising from lobular structures. Infiltrating ductal carcinoma accounts for the largest group of breast cancers, representing 65 to 80 percent of cases.10 The classic mammo-graphic presentation of infiltrating ductal carcinoma is a high-density mass with spiculated margins (Figure 3-3A). Sonographically, this lesion is typically seen as a shadowing, hypo-echoic mass with irregular margins (Figure 3-3B). The presentation of infiltrating ductal car Infiltrating lobular carcinoma is the second most common type of invasive breast cancer, representing approximately 15 percent of cases.10 It has a higher rate of multicentricity and bilaterality than infiltrating ductal carci-noma.11 Infiltrating lobular carcinoma is known for its insidious nature, delaying clinical and mammographic diagnosis. The subtle nature of infiltrating lobular carcinoma is thought to be due to its pattern of...

Primary Chemotherapy for Advanced CRCs 5FU

Developed in 1957, 5-FU represents one of the earliest examples of a rationally designed drug, and now, almost five decades later, it still remains the base of almost all CRC chemotherapy regimens. Following metabolic activation to 5-fluoro-2'-deoxyuridylate (FdUMP), this fluorinated pyrimidine combines with methylenetetrahydrofolate (CH2FH4) to form a ternary complex with thymidylate synthase (TS) thus interfering with DNA synthesis by inhibiting the conversion of deoxyuridylate to thymidy-late. Additional mechanisms of action include direct incorporation into ribonucleic acid (RNA) to interfere with RNA transcription and, to a lesser extent, direct incorporation into deoxyribonucleic acid (DNA).

The Search for a Human Breast Cancer Virus

One of the premises of Virus Cancer Program was that comparable oncogenic retroviruses and oncogenes would be found in humans (Gardner, 1994b). This rekindled the long-standing search for the elusive human breast cancer virus. This search deserves separate mention since the possibility has long fueled the imagination and provided a source of financial support. From the virological viewpoint, each technical advance in virology and molecular biology has led to reports of virus-like footprints that, when pursued to their logical end, have never led to a satisfactory conclusion. Improved tissue culture techniques in the 1970s brought claims of a human breast cancer virus that was proven by Walter Nelson-Rees to be the result of a worldwide cross contamination by HeLa cells containing the Mason-Pfizer Virus (Nelson-Rees et al., 1981). Molecular hybridization, particularly under relaxed conditions, led to a series of suggestions of endogenous human sequences (May and Westley, 1989 Westley...

Role Of Surgery After Induction Chemotherapy

Since the mid-1970s, patients with LABC treated at The University of Texas M. D. Anderson Cancer Center have received three to four cycles of doxorubicin-based combination chemotherapy prior to local therapy local therapy is followed by the completion of systemic therapy and irradiation. Between 1974 and 1996, patients with LABC were treated in four trials addressing four major concerns about the use of induction chemotherapy (1) whether tumor progression will occur during induction chemotherapy, rendering the tumor unre-sectable even with radical surgery (2) whether operative morbidity is increased after induction chemotherapy (3) whether the histologic staging information obtained from the surgical specimen after induction chemotherapy maintains its prognostic correlations with survival (4) and whether breast conservation therapy with or without an axillary node dissection is feasible and safe in patients with LABC. In the first clinical trial at M. D. Anderson Cancer Center (1974...

Genetics Natural History and DNABased Genetic Counseling in Hereditary Breast Cancer

The extraordinary advances in molecular genetics during the past decade have established beyond doubt that there is a Mendelian inherited basis for a subset of virtually all forms of cancer.1 Specifically, more than 30 hereditary cancer syndromes have been shown to harbor germ-line mutations. These culprit molecular genetic factors include oncogenes such as the RET proto-oncogene for the multiple endocrine neoplasia type 2 syndromes, the mismatch repair genes (hMSH2, hMLHl) in hereditary nonpolyposis colorectal cancer (HNPCC) of the Lynch I and Lynch II syndrome variants, and tumor suppressor genes. Examples of the latter include APC, which predisposes to familial adenomatous polyposis (FAP), and BRCA1 and BRCA2 mutations in hereditary breast cancer, the subject of this chapter. In the United States in 1999, it was projected that 176,300 new cases of carcinoma of the breast would be diagnosed, and 43,700 would die from this disease.2 The current authors estimate that approximately 10...

Chemotherapy in the HAART

In the HAART era, more recent standard chemotherapy regimens have been reported without excessive toxicity due to restored immunity.90 The AIDS Malignancy Consortium (AMC) reported using, in 65 patients, reduced doses of cyclophosphamide and doxorubicin, combined with vincristine and prednisone (modified CHOP, mCHOP) and full doses of CHOP combined with G-CSF with concomitant HAART. Complete response rates were 30 and 48 in the reduced-and full-dose groups, respectively.94 No long-term outcomes were reported in this study. Other studies of CHOP-based chemotherapy and concurrent HAART have resulted in median survival of 2 years.53,95 Risk-adaptive chemotherapy has also been studied comparing the post- to pre-HAART era. 485 HIV-infected individuals were assigned randomly to chemotherapy after risk stratification based on an HIV score (comprising performance status, prior AIDS, and CD4-positive cell counts < 100 mm3).Two hundred eighteen good risk patients (HIV score 0) received...

Chemotherapy

Systemic chemotherapy is often indicated to control disseminated breast cancer and relieve symptoms. While prolonged remissions may be achieved, there is no evidence that metastatic breast cancer can be cured by chemotherapy. Thus, the ultimate goals are again palliative, and the toxicity of chemotherapy must be carefully weighed against a realistic appraisal of benefits. With this caveat, chemotherapy is commonly indicated as frontline therapy for metastases to liver or lung, those arising from estrogen receptor-negative tumors, and those that fail to respond to initial or subsequent hormonal treatments. There are a wide variety of chemothera-peutic agents that show some activity against metastatic breast cancer. Response rates are affected by site of disease, with soft tissue metastases typically most responsive, and liver metastases least responsive, to many agents. Prior treatment history has a major effect on the likelihood of response, due to the phenomenum of pleiotropic drug...

Cancer Family History and Mutation Search

The search for a germ-line mutation should be performed only on families with substantial evidence of a hereditary cancer syndrome. Therefore, to establish a hereditary breast cancer syndrome diagnosis, a detailed collection of a patient's cancer family history, with as much pathologic corroboration as possible, is mandatory. The family history may potentially constitute the most cost-beneficial component of a patient's medical workup its collection and evaluation in the typical clinical setting, however, remains notoriously neglected.16,17 This problem was well documented by David and Steiner-Grossman17 through a survey of 76 acute care, non-psychiatric hospitals in New York City. Only four of the 64 reporting hospitals indicated that family history information was reported in their medical records. Such serious omissions must be resolved in order to enhance cancer control. Otherwise, the opportunity to search for germ-line cancer prone

Genotypephenotype Differences

More than 200 different BRCA1 germ-line mutations have been identified in HBOC families. Certain types of these mutations may give rise to differing patterns of cancer occurrence. For example, Gayther and colleagues19 suggest that the position of the BRCA1 mutation has a significant influence on the ratio of breast to ovarian cancer in HBOC kindreds. Specifically, they reported that mutations in the 3' third of the gene are associated with a lower proportion of ovarian cancer. However, these findings must be reviewed cautiously. Serova and colleagues20 were unable to confirm these findings. However, the findings of the latter did suggest that the risk of ovarian cancer is greater in families with mutations associated with reduced RNA levels. In the case of BRCA2, Gayther and colleagues21 found that truncating mutations in families with the highest risk of ovarian cancer relative to breast cancer are clustered in a region of approximately 3.3 kb in exon 11 (p .0004). Further research...

Usefulness of Mammography

The practice of mammography can be divided into three categories screening, diagnosis and surveillance. Screening involves examination of asymptomatic women in an attempt to detect breast cancer before a lesion is palpable. Diagnostic mammography is performed on women having symptoms or physical findings suspicious for breast cancer or for further mammographic workup of a nonpalpable finding detected at screening. Surveillance mammog-raphy provides follow-up of a breast that has been treated for cancer. The usefulness of mammography in the symptomatic patient is undisputed mammography is primarily used to demonstrate the presence of breast cancer and, specifically to indicate the size, location and extent of tumor. There is also considerable evidence indicating the ability of mammography to detect nonpalpable cancer. In addition, randomized controlled trials of screening mammography have demonstrated a significant decline in breast cancer mortality among screened women age 50 and...

Radiation Effects And Brca1 And Brca2 Mutations

In a study by Chabner and colleagues45 of 201 patients, 29 of whom had positive family histories of breast cancer (a mother or sister previously diagnosed before the age of 50 years, or ovarian cancer at any age) and who had undergone breast-conserving surgery and radiation therapy for early-stage breast cancer, there was no evidence associated with a higher rate of local recurrence, distant failure, or second (nonbreast) cancers in young women with a family history (FH) suggestive of inherited breast cancer susceptibility compared with young women without an FH. As expected, the patients with a positive FH showed an increased risk of contralateral breast cancer. This matter of contralateral breast cancer must be given careful consideration when counseling women with positive family histories who are considering the option of breast conserving surgery and radiation therapy versus modified radical mastectomy. Given these findings, Chabner and colleagues45 conclude that young women can...

Prophylactic Mastectomy

Tomy on a retrospective cohort study of all women with a breast cancer-positive family history who underwent bilateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. These women were divided into high-risk versus moderate-risk groups based on their family history. Those at high risk showed pedigrees consistent with a single-gene, autosomal dominant predisposition to carcinoma of the breast, whereas those at moderate risk showed positive family histories that did not meet these high-risk criteria. To predict the number of breast cancers expected in these two groups had prophylactic mastectomies not been performed, the researchers used a nested-sister control study for the high-risk group and the Gail Model for the moderate-risk group. Their findings were based upon 693 women with a family history of breast cancer (214 high-risk and 425 moderate-risk) who had bilateral prophylactic mastectomies. Their median follow-up was 14.4 years, while the median age at...

Unifying The Four Modalities

The importance of developing alternative breast cancer imaging modalities is that they may access new mechanisms of physiological contrast. Further, there may be synergistic effects when the four approaches discussed in this text are used as complements to each other rather than in isolation. This mul-timodality approach is an important theme, as it is unlikely that any single breast-imaging method will be superior across the whole spectrum of women receiving clinical breast care.

Potential For Targeted Brca1brca2 Mutation Therapy

In addition to identifying cancer risk status through mutations such as BRCA1 and BRCA2, this knowledge has the potential to provide individualized highly-targeted molecular genetic therapies based upon mutation discoveries.56 Specifically, once the functions of cancer susceptibility genes have been identified, knowledge as to how such gene-determined biochemical functions can be employed for targeted radiation and chemotherapy should emerge.

Familial and Genetic Factors

Identification of cohorts at genetic risk for cancer is an appealing concept because it may offer the opportunity to explore the steps in breast carcinogenesis, from the inheritance of a predisposing mutation through the development of preinvasive lesions or overt malignancy. However, germline genetic changes are rare and reported in only a small proportion of women who will eventually develop breast cancer.15 Breast cancer attributed to a family history of the disease has been reported to account for 6 to 19 percent of all cases of breast cancer. Hereditary breast cancers, which constitute a proportion of these cases, are characterized by early onset, a high incidence of bilateral disease, association with other malignancies, and autosomal dominant inheritance. Genetic-linkage studies of families with multiple members with breast cancer have allowed major improvements in our understanding of the genetic alterations associated with hereditary predisposition. Such studies led to the...

Environmental Radiation Exposure

Epidemiologic observations suggest that exposure of breast tissue to ionizing radiation is associated with an increased risk of breast cancer. In particular, an increased risk of breast carcinoma has been clearly documented in young women that have survived atomic bombs, in patients who have undergone repeated fluoroscopies (eg, in patients with tuberculosis), and in patients treated with radiation for postpartum mastitis, thymic enlargement, and Hodgkin's disease.26-37 The hypothetical risk of breast cancer derived from prolonged screening needs to be mentioned. Using a risk estimate provided by the Biological Effects of Ionizing Radiation (BEIR) V Report of the National Academy of Sciences and a mean breast glandular dose of 4 mGy from bilateral mammography, with two views per breast, one can estimate that annual mammography of 100,000 women for 10 consecutive years beginning at age 40 years will result in, at most, 8 breast cancer deaths during their lifetime. On the other hand,...

Prophylactic Oophorectomy andor Hysterectomy

Several studies have documented lower breast cancer incidence among women who underwent oophorectomy at a young age. The effect of hysterectomy on breast cancer risk is less clear, but it has been postulated that hysterectomy may have some secondary effects by affecting ovarian blood flow and ovulation. Schairer and colleagues evaluated 15,844 women undergoing surgery in the Uppsala health care region of Sweden and found a 50 percent reduction in breast cancer risk in those women who underwent bilateral oophorectomy prior to age 50 years, compared with the risk of the background population.146 Hysterectomy alone had no consistent association with change in breast cancer risk. In a case-control series from Italy, women who underwent premenopausal oophorectomy with hysterectomy or hysterectomy alone had reduced relative risk of developing breast cancer (0.8 and 0.7, respectively).147 However, given the importance of the ovarian function in maintaining cardiovascular and bone health,...

Benefits Of Estrogen Replacement Therapy

Over the last two decades, overwhelming evidence has been accrued demonstrating that postmenopausal estrogen replacement protects against ischemic heart disease, osteoporosis, deterioration in cognitive function, colorectal cancer, and provides relief from vasomotor symptoms and urogenital atrophy. Multimodal-ity screening has resulted in an increase in the incidence of breast cancer diagnoses this increase, however, reflects more frequent detection of early-stage breast cancer. Because breast cancer survival is inextricably linked to early diagnosis, there are now more breast cancer survivors than ever. Morbidity and mortality associated with estrogen deprivation present serious health concerns. The risk benefit ratio of estrogen replacement therapy (ERT) is an appropriate consideration for all patients.

Radiation Risk Versus Benefit of Mammographic Screening

In this Section, a comparison is presented between the risks of breast cancer induced by radiation exposure of the breast during mammography and the possible reduction in breast cancer mortality arising from mammographic screening. Risks are estimated in terms of the BEIR V models (NAS NRC, 1990), presented above, and benefits are considered in terms of various assumed reductions in breast cancer mortality rates as a consequence of mammo-graphic screening. The benefit risk model uses standard life table techniques to estimate the numbers of breast cancer cases and breast cancer deaths that will occur in a population of 100,000 women under various mammographic screening scenarios. The numbers of cases or deaths are those which will occur from the age at which a woman is first screened, under a particular scenario, to the end of life. Single-year age-specific breast cancer incidence, breast cancer mortality and all other cause mortality rates were estimated by linear interpolation from...

Dietary Interventions

Epidemiologic observations of large international differences in the incidence of breast cancer have provided a basis for formulating hypotheses on a possible relation between diet and the development of cancer. The age-adjusted incidence of breast cancer varies from 22 per 100,000 in Japan to 68 per 100,000 in the Netherlands.116 The ratio of breast cancer mortality between the United States and Japan is 3 1 for premenopausal women and 8 1 for postmenopausal women.117 These important differences may possibly be related to fat intake and total calories in the diet. Clinical data collected from case-control studies have demonstrated a positive correlation between diets high in fat and meat and breast cancer.118-122 Experimental studies have shown that omega-6 polyunsaturated fatty acids (PUFAs) contained in high-fat diets promote both mammary tumorigenesis and cell proliferation in chemically induced mammary tumors, whereas omega-3 PUFAs, contained in fish oil, can inhibit these...

Understanding Patterns Of Relapse And Failure

There are multiple effective treatments of breast cancer. Which one is most appropriate to increase survival and cure rate after primary therapy of early disease is dependent on the nature of the failure. Is it due to inadequate control of the primary tumor, regional spread, or distant metastases The Halstedian view of breast cancer spread was that of a prolonged period of local regional disease before systemic dissemination. By implication, failure to cure might be due to incomplete surgery. As discussed in Chapter 11, multiple studies have failed to confirm the survival benefit of more aggressive versus less aggressive surgery. A recent meta-analysis of 3,400 women in randomized trials of more versus less extensive surgery found no difference in 10-year survival between the two approaches.5 This was true whether or not the patients had axillary nodal involvement. Radiation therapy is another approach to local and regional control. If the Halstedian paradigm were true, local regional...

Mastectomy and Breast Conservation Therapy Equivalent Survival

Several randomized clinical trials have confirmed equivalent survival data when lumpectomy and breast radiotherapy are compared to modified radical mastectomy for early-stage invasive breast cancer. Local recurrence rates after conservative surgery and radiotherapy range from 3 to 19 percent (Table 13-1).14-20 It should be noted that the study from the NCI had the highest rate of local recurrence but did not require negative pathologic resection margins, the significance of which is discussed below. This same study was the only trial to show a significant advantage to mastectomy with respect to local recurrence. Despite a broad range of entry criteria (acceptable tumor size ranged from 2 to 5 cm), the data are remarkably consistent. The most important finding was the equivalent overall survival between treatment arms in all studies. Local recurrence in the mastectomy-treated patients ranged from 4 to 14 percent. Equivalent survival between extensive surgery and limited surgery plus...

Historic Overview Identification of Novel Cancer Markers

The first widely studied cancer-associated marker was carcinoembryonic antigen (CEA). It was detectable in tumors as well as body fluids and generated great excitement as a marker for the diagnosis or monitoring of cancer. It is expressed by adenocarcinomas (including breast cancers) however, benign epithelium and inflammatory states produce CEA as well. The challenges in CEA research were making reagents and assays that were specific for CEA, quantitating the protein in human tissues and body fluids, determining the associations with clinical and disease parameters, and better definition of CEA biology and structure. We know now that CEA is a member of a large family of proteins with homology to other cross-reacting antigens.52-55 Many of the early studies used nonspecific reagents and generated conflicting results. The CEA has shown limited usefulness in breast cancer immunodiag-nostics and as a marker of disease progression. Because it is not part of a critical molecular pathway,...

Palliative Therapy Against Overt Macroscopic Tumor And Potential Eradication Of Occult Microscopic Disease

A basic assumption underlying adjuvant systemic therapy of early breast cancer is that those therapies that may be only palliative against bulky macroscopic metastases might be curative against microscopic disseminated tumor that is assumed to be present in high-risk patients. To develop effective adjuvant systemic therapy of early disease, one must first identify effective and safe therapies for advanced-stage breast cancer. Systemic therapy for overt advanced breast cancer began 100 years ago when Beatson observed shrinkage of locally extensive breast cancers after oophorectomy in premenopausal women.6 This phenomenon is based on the trophic effect of estrogen on approximately half of all breast cancers studied. Removal of the ovaries leading to a drop in endogenous estrogen levels in younger women can arrest cancer growth and result in regression. Another approach to depriving breast cancers of estrogen effects is to block estrogen binding to the protein, estrogen receptor (ER), in...

Screening and Diagnostic Imaging

Mammography is currently the best available screening modality for early detection and diagnosis of breast cancer. Periodic examination of asymptomatic females with mammo-graphy has been shown to reduce breast cancer mortality.1 In accordance with the American Cancer Society recommendations, the available scientific data suggest a benefit from annual mammographic screening of all women beginning at the age of 40 years, combined with annual physical examination and monthly breast self examination.2 For women between 20 and 39 years of age, the ACS recommends a breast physical exam every three years and monthly breast self exam. Patients with a first-degree premenopausal relative diagnosed with breast cancer may consider beginning annual screening examinations 10 years prior to the age at which the relative was diagnosed, in an attempt to benefit from early detection.3 Screening mammography evaluates asymptomatic women with the goal of discovering unsuspected breast cancer at an early...

Imaging Studies of the Liver

There have been no prospective studies comparing sensitivity and specificity of CT and MRI evaluations in the postoperative surveillance of breast cancer patients. However, on the basis of evaluation in preoperative breast and lung cancers, it is safe to conclude that in the absence of symptoms and abnormal liver function tests, these imaging techniques will be of little or no value. The Italian GIVIO investigators performed liver echography in their intervention group. In that study, 6.5 percent of patients had their first recurrence diagnosed by liver echography, versus 6.1 percent in the control group, who had echography because of abnormal examination and or hepatic function tests.11 Based on these studies, it can be concluded that routine imaging techniques for detecting liver metastasis are not warranted. Table 16-2 summarizes recommendations for follow-up of breast cancer patients who have completed their primary therapy, and, when appropriate, adjuvant chemotherapy.

Diagnostic Evaluation

Although the surgeon is sometimes the first physician that encounters the patient with breast cancer, this diagnosis may be initially suspected by primary care physicians or other specialists. Although few of these physicians will be directly involved in the diagnostic procedures, all should be familiar with the key issues relevant to the initial evaluation of women with suspected breast cancer.

Ductal Carcinoma In Situ

Although the primary role of adjuvant systemic therapy is to treat occult distant disease, there may also be a local benefit, at least in ductal carcinoma in situ trial (DCIS). The NSABP trial B-24 randomized 1,804 women with DCIS treated with lumpectomy plus radiation to no further therapy or to 5 years of tamoxifen.52 At 5 years, tamoxifen decreased the risk of the development of invasive breast cancer in the treated breast by 47 percent (2.1 versus 3.4 in control, p .04) and of all breast cancer events (ipsilateral and contralateral) by 34 percent (8.8 versus 13 in control, p .007).52 These results apply only to women who had lumpectomy radiation for DCIS. They are not relevant to women treated with mastectomy. While the absolute magnitude of the benefit was small, certainly tamoxifen should be considered in many women with DCIS treated with breast conservation, particularly those with high-risk pathology.

Evaluation Of The Augmented Breast

The presence of breast implants causes technical problems that impair the ability to detect breast cancer by mammography. The radiopaque implant blocks x-ray transmission, which limits the imaging of breast tissue. Implants compress breast tissue against the skin which can obscure a significant amount of anterior breast tissue on conventional mammographic images. Implants also diminish the compressibility of the breast, particularly if there is capsular contracture.

Histopathology of Malignant Breast Disease

The basic classification of malignant breast diseases has remained relatively unchanged since the most recent WHO revision in 1982.1 These conditions can be broadly divided into epithelial and nonepithelial lesions, with separation of the former into in situ and invasive tumors (Table 5-1). Although recent studies have shed new light onto our understanding of the basic biology and natural history of breast cancer, this traditional classification still retains its relevance for clinicians involved in the diagnosis and treatment of malignant breast disease.

Adjuvant Therapy Validated In Randomized Controlled Trials

Effective therapies of advanced breast cancer were long known and anecdotally used after surgery for early breast cancer, but their value as adjuncts to primary therapy was difficult to assess. Unlike in advanced disease, where tumor shrinkage after systemic treatment can be determined directly by observation or radiographi-cally, when used to increase survival after treatment of early stage disease, there are no direct determinants of effectiveness. Cure in an individual patient with early-stage disease may have been achieved as a result of the systemic therapy or might have occurred even if it had not been given as a result of the local treatment. Recurrence may be a sign of failure of adjunctive therapy but might have been delayed because of it. The only way to truly evaluate the usefulness of additional treatments after primary therapy of breast cancer is by large RCTs. Initially, those trials randomized women with high-risk, early-stage disease to surgery alone or to surgery plus...

Breast Reconstruction

In contrast to the 1960s when silicone implants were the mainstay of breast reconstruction, patients in the 1990s may choose from an impressive spectrum of reconstructive options. Techniques, instruments, and materials have evolved that provide all patients, regardless of age, stage, previous treatment, or laterality, choices that may optimally represent their desires and expectations. Breast cancer awareness has increased the sophistication of patients, however, it remains the plastic surgeon's responsibility to educate patients and coordinate expectations and outcome. Increased detection of breast cancer has paralleled improved techniques and availability of screening mammography, an increased female population, and the impact of changes in the age of childbearing, menarche, and menopause. Today, ductal carcinoma in situ (DCIS) represents 15 to 20 percent of all breast cancer cases 1 it is treated by either localized resection or total mastectomy. Genetic testing and better...

Magnetic Resonance Imaging Of The Breast

High-spatial-resolution MR imaging of the breast is evolving as an important adjunctive diagnostic tool for the detection, characterization, staging, and monitoring of breast cancer. Contrast-enhanced MR imaging may allow more accurate preoperative evaluation of primary malignant breast lesions that may be underestimated or not seen on mammography or by ultrasonography. Magnetic resonance imaging has revealed unsuspected multifocal, multi-centric, diffuse, and bilateral disease in patients with a solitary mammographic lesion.39-41 The sensitivity of contrast-enhanced MR imaging approaches 100 percent in the detection of invasive breast cancer when compared to mammography and physical examination.35,39,41 The specificity of breast MR imaging ranges from 37 to 97 percent.39,41,42 This wide range is attributed to the overlap in contrast enhancement of benign and malignant lesions. Higher specificity for breast MR imaging can be achieved using a dynamic contrast-enhanced technique with...

Combined Chemohormonal Therapy

The 1995 EBCTCG overviews looked at the relative benefits of adjuvant combined chemo-hormonal therapy versus single-modality treat-ment.19'31,38 There was a suggestion that in women aged 50 to 69 years, tamoxifen plus chemotherapy decreased the annual risk of death by 10 percent compared with tamoxifen alone.31 The issue was prospectively studied in newer trials. The NSABP, SWOG, and the International Breast Cancer Study Group, each found benefit in their studies of combined therapy versus tamoxifen alone in postmenopausal women 44-46 the National Cancer Institute (NCI) of Canada did not.47 While it is premature to suggest that all postmenopausal women with receptor-positive cancer should receive chemotherapy and tamoxifen certainly, it is appropriate in selected high-risk women under the age of 70 years. The best way to combine the two, simultaneously or sequentially, still remains unresolved. For women under the age 50 years, the 1995 overview suggested that the addition of...

Vasomotor Instability

The menopausal state most commonly produces vasomotor instability and genital organ atrophy. Vasomotor symptoms affect 70 percent of postmenopausal women but only about 30 percent seek medical assistance. For 25 percent of menopausal women, these symptoms may persist for > 5 years and may be lifelong in others. Vasomotor instability is more commonly termed hot flushes or hot flashes. The frequency, severity, or diurnal variation with which hot flushes occur can result in significant disruptions of sleep and daytime function. Menopausal symptoms are the most common side effect associated with the use of adjuvant chemotherapy for breast cancer, with approximately two-

Clinical Presentation And Evaluation

The clinical features of male breast cancer have recently summarized.55 Signs and symptoms of male breast cancer are shown in Table 14-3. The mean age of patients presenting with this disease as noted above, is usually in the late 50s to mid-60s, with a range from the mid-20s to the early 90s. The most common presenting complaints are related to a breast mass, usually occurring in > 70 percent of cases, and axillary adenopathy, occurring in 30 to 50 percent of cases. For pure DCIS, a subareolar mass and nipple discharge were the two most common Table 14-3. SIGNS AND SYMPTOMS OF MALE BREAST CANCER symptoms in a recent series, occurring in 58 and 35 percent of patients, respectively.43 In virtually all series, there is a report of significant delay in diagnosis of breast cancer in men. In early series, the mean duration of symptoms was > 14 months. In recent series, the mean duration is declining to a range of 3 to 6 months.48,50,52,54 There is a history of trauma in many series,...

Treatment Of Localized Disease

The treatment of male breast cancer localized to the breast and axillary nodes is mastectomy with axillary lymph node dissection.55 In several recent series, modified radical mastectomy was the most common procedure performed, with from 34 to 76 percent of patients treated in this fashion.8,20,50-52,54,65 In one multi-institutional survey, 82 percent of patients diagnosed since 1986 were treated by modified radical mastectomy.54 Of 242 patients treated in the Department of Veterans' Affairs, 51 percent underwent modified radical mastectomy.8 Other surgical procedures reported in these patients include radical mastectomy, simple mastectomy, and lumpectomies. ing mastectomy versus lumpectomy.52 Axillary dissection is considered part of the local-regional treatment of breast cancer. Cutuli and colleagues reported a statistically significant difference in the regional nodal recurrence rate of patients undergoing axillary dissection compared to those without dissection 1.2 percent of 320...

Image Directed Breast Biopsy

The recent increase in the detection of nonpalpable breast abnormalities requiring further evaluation is thought to be the direct result of more favorable participation in mammography screening. Appropriate diagnostic work-up will lead to a relative increase in lesions that are of sufficient risk to warrant a biopsy. In fact, it has been estimated that approximately 1.2 million breast biopsies are performed per year in the United States. Unfortunately, an average positive predictive value for mammog-raphy of 20 percent (range 15 to 35 ) will yield a significant number of biopsies performed for benign disease.1-4 If 5 women are identified on the mammogram to have a lesion requiring biopsy, only 1 of these 5 women will be found to have breast cancer. Therefore, if traditional methods for histologic confirmation are used, all 5 women would proceed to the operating room for an open surgical biopsy after first having had wire localization in the radiology suite. Image-guided percutaneous...

Ipsilateral Breast Tumor Recurrence

And 1 (3 ) was stage IV However, node information was available for only 5 of the 35 patients with invasive recurrence because 30 patients initially underwent axillary dissection with the treatment of their primary tumor. Thus, some of the remaining 30 patients were probably understaged. At 8-year follow-up after treatment of the 35 patients for local invasive recurrence, the probability of developing distant metastases was 27 percent and the breast cancer-specific mortality rate was 14.4 percent. The 8-year breast cancer mortality rate for 448 patients that had breast conservation treatment for DCIS was 2.1 percent. The results indicated that, regardless of treatment choice, the overall mortality rates were low.

Other Hormonal Approaches

Several other hormonal therapies have activity against metastatic breast cancer and have been evaluated as adjuvant therapy in early disease. Toremifene (Fareston) is a derivative of tamox-ifen with a similar mechanism of action and activity against disseminated disease.7 It is being evaluated in randomized trials against tamoxifen as adjuvant therapy in older women. Progestins lower endogenous estrogen levels in postmenopausal women and cause tumor regression in many women with advanced disease.7 Medroxyprogesterone has been studied as adjuvant therapy in randomized trials, with negative results.41,42 Aromatase inhibitors (AI) inhibit the enzyme that catalyzes the conversion of androgen to estrogen. They, too, lower serum (and intracellular) estrogen levels in older women and are effective hormonal therapies of metastatic breast cancer.7 Aminog-lutethimide, one of the first-generation aro-matase inhibitors, however, was no better than placebo in an adjuvant trial after surgery in...

Strategies For Improving Systemic Therapy

Advances in the treatment of LABC are largely dependent on improvements in systemic chemotherapy. Two major strategies to improve systemic therapy include improved selection and individualization of chemotherapy regimens and the development of novel targeted therapies. If the chemosensitivity of a specific breast cancer could be predicted before or soon after the initiation of chemotherapy, an optimal treatment regimen could be designed for that tumor. One possible way to predict chemosensitivity is to measure levels of cellular proteins associated with drug resistance, including MDR1 (mul-tidrug-resistance protein, or P-glycoprotein), MRP (multidrug resistance-associated protein), glutathione S-transferase, and dihydrofolate reductase.50 Although MDR1 is often not expressed in early-stage breast cancer, it is detectable at a high frequency in patients with LABC 51 and appears to correlate with a poor response to chemotherapy. However, the other proteins associated with drug...

Benefits Versus Toxicity And Risks Of Therapy

The acute toxicities of adjuvant systemic therapy of early breast cancer are significant but generally well tolerated and are easily justified given the potential benefit. The toxicities of chemotherapy can be divided into those of the CMF-like regimens and those of the doxoru-bicin regimens. All chemotherapies used as adjuvant treatment cause significant myelosup-pression, with leukopenia generally clinically more significant than anemia or thrombocy-topenia. In the NSABP trials of classic CMF x 6, the incidence of neutropenia less than 2,000 was 10 percent and severe infection about 1 percent.21 With AC x 4, it is 4 percent severe neutropenia and 2 percent severe infec-tion.21 With 6 months of CAF, the risk of leukopenia and infection is higher. Thrombocy-topenia is seen in less than 1 percent of patients in most regimens.21 Doxorubicin-containing regimens are more emetogenic than CMF however, the incidence of severe vomiting is rapidly dropping with the introduction of serotonin...

Benefits and Risks of Mammography

Screening is the periodic examination of a population to detect previously unrecognized disease. The major goal of breast cancer screening is to reduce breast cancer mortality through detection of earlier-stage disease. Earlier detection also provides a wider choice of therapeutic options. Mammography can frequently detect breast cancer at a relatively early stage when tumors are too small to be palpable. Table 7.1 Breast cancer detection by the BCDDP according to lesion size and modality findings.a Breast Cancer Sizeb Table 7.1 Breast cancer detection by the BCDDP according to lesion size and modality findings.a Breast Cancer Sizeb 7.1.3 Breast Cancer Survival Rates Survival rates among breast cancer patients depend in large part on two related factors tumor size and stage at time of diagnosis. Smaller cancers with no histologic evidence of spread to the regional lymph nodes have the best prognosis. The 20 y relative survival rates in the BCDDP were 80.5 percent (overall), 85.1...

Nuclear Medicine Techniques For Breast Imaging

Breast cancer imaging has also been performed using positron emission tomography (PET) imaging of a structural analog of glucose, fluorodeoxyglucose (FDG). The sensitivity and specificity for PET scanning of the breast range from 70 to 90 percent and 85 to 95 percent, respectively.47,48 As with scintigraphic imaging, lesions < 1 cm are not reliably detected with PET imaging. Improvements in the ability to detect small lesions will be necessary before clinical utility of scintigraphy and PET can be proven.

Growth Factors and Receptors

IMPORTANT MARKER GROUPS IN BREAST CANCER The erbB-2 overexpression amplification is a complex process,67-69 which occurs in approximately one-third of invasive and up to two-thirds of in situ carcinomas.70-77 The erbB-2 alterations have been associated with a poor prognosis in breast cancer patients,17 50 78-89 although it is usually less predictive of outcome than lymph node metastases. A resurgence of interest in erbB-2 as a breast cancer marker has recently occurred because erbB-2 alterations may predict chemore-sponsiveness818385 and the FDA has recently approved the drug Herceptin (Trastuzumab, Genentech, Inc.), which targets erbB-2. Cancers without erbB-2 alterations have two copies of the gene (unless deletions have occurred) and encode low levels of protein. All normal cells and the majority of breast cancer cells bear two copies of the erbB-2 gene and produce low levels of the encoded protein p185. Assays to evaluate erbB-2 generally measure either gene copy number...

Unusual Breast Pathology

This chapter reviews clinical and pathologic features of uncommon breast malignancies. The majority of the data used in the course of writing the chapter was obtained from small studies of specific tumor subtypes, or has been gleaned from larger studies that included several types of more common breast cancers. Unfortunately, there is often insufficient information available to draw absolute conclusions regarding therapy and prognosis. Much of the data cited was collected prior to the widespread use of breast conservation. For this reason, the vast majority of patients studied were treated using mastectomy. The reliance on mastectomy has resulted in a lack of information regarding the natural history and radiosensitivity of many of the tumors presented. Therefore, the risk of local recurrence for patients with rare breast malignancies opting for breast conservation is unclear. There is, however, no reason to suspect a significant difference in the risk of local recurrence in this...

Skinsparing Mastectomy

Toth and Lappert first described skin-sparing mastectomy (SSM) in 1991.9 The technique is indicated for patients with early stage (I and II) breast cancer, patients managed with prophylactic mastectomy, and in attempts to facilitate a highly esthetic outcome through maximal skin preservation (Figure 11-1). Incisions are planned that will remove the breast, nipple-areolar complex, adjacent biopsy scars, and the skin over more superficial tumors. Kroll and colleagues in rate was 4.8 percent in the former group and 9.5 percent in the latter native skin flap necrosis occurred in 10.7 percent of the SSM patients and in 11.2 percent of the non-SSM patients.13 Because local recurrence after SSM is low and the likelihood of local control and survival are high, SSM with immediate reconstruction is an acceptable treatment for breast cancer.

Management of the Axilla

Just as treatment of the primary tumor of the breast has evolved from a single, radical operation for all scenarios to a more directed approach consisting of lumpectomy, the standard axillary dissection is quickly being replaced by sentinel lymphadenectomy. Introduced by Morton and colleagues in 1992 for the treatment of melanoma,39 this technique was quickly applied to breast cancer.4041 Like lymphatic mapping for other disease sites, the sentinel lymph node is identified through the constant anatomic relationship between a tumor and draining lymphatics. Conceptually, each specific area in the breast drains to a sentinel lymph node which may be located anywhere within the axilla or internal mammary chain (Figure 9-10). Larger tumors may have more than one draining lymphatic (Figure 9-11). The sentinel lymph node biopsy continues to be refined and defined for patients with early breast cancer in several studies, it has been demonstrated to yield reliable correlation to an axillary...

Treatment Of Metastatic Disease

Many men with breast cancer present with metastatic disease, ranging from 11 to 16 percent in several recent series.20'46'47'50'54 The pattern of spread in male patients is similar to that seen in female patients including local regional recurrences and metastases to bone, lung, liver, skin, and other areas.9,20,50,51,53 The first-line palliative therapy used by most authors is hormonal procedures have been reported in > 50 percent of cases.87 Other hormonal manipulations, including androgen therapy and gonadotropin-releasing hormone agonist analogue therapy have been reported.55 Systemic chemotherapy may be considered as a second-line palliative treatment, with an overall response rate of 30 to 40 percent.28,62,87,90-92 Combination chemotherapy, such as CMF or doxorubicin-containing regimens, have been reported in various series

Carcinoma Of The Breast With Endocrine Differentiation

Rarely, tumors of the breast may undergo endocrine metaplasia and have the ability to produce ectopic hormones such as human chorionic gonadotropin (HCG), calcitonin, adrenocorti-cotropin, and epinephrine. Endocrine differentiation may arise in the setting of ductal carcinoma in situ, small-cell undifferentiated carcinoma, mucinous carcinoma, lobular carcinoma, and infiltrating ductal carcinoma.346 Rarely, the microscopic architecture of a breast cancer with endocrine differentiation may mimic the histo-logic structure of nonmammary tissue that contains the ectopic hormone being produced.

Identification Of Populations At High Risk Of Relapse

Although not every women with early stage, localized breast cancer is rendered cancer free by local treatment, many women are. It is critical, if additional treatments are to be used, that they be directed at women at highest risk of recurrence. Indiscriminate administration of adjunctive therapies runs the risk of unnecessarily exposing those already cured to toxicity, morbidity and, with some aggressive approaches, even mortality from treatment. Choice of patients to be treated is critical in the development of successful adjuvant therapy. For women with early stage, operable breast cancer, the single most important prognostic feature for recurrence and death is the presence or absence of tumor metastases in the axillary lymph nodes.1,2 Patients with no axillary nodal metastases have a 70 to 75 percent chance of long-term disease-free survival (DFS) when treated with surgery alone. Patients with any number of nodal metastases have a 25 to 30 percent chance of long-term survival.3...

The Choice Of Adjuvant Therapy And The Biology Of The Tumor And Of The Patient

Despite the successes of adjuvant chemotherapy and hormonal therapy, many patients that receive such treatments have recurrences and die. To optimize results, when choosing treatment, tumor and patient biology must be taken into account. This is most apparent in the use of hormonal therapy. Although there is a small but real response rate with tamoxifen in metastatic hormone receptor-negative breast cancer, the 1995 meta-analysis found no significant benefit to adjuvant tamoxifen in women with receptor-poor tumors.31 It is, therefore, critical that hormone receptor be measured in any patient with newly diagnosed breast cancer.4 Although there was some controversy in the past as to whether hormone receptor status is also of value in predicting response to chemotherapy, it is now known that no such relationship exists.19 On the other hand, there is preliminary data that suggest the presence of an overexpressed c-erbB-2 oncogene in breast cancers may have predictive value in the choice...

Evolving Markers Based on Cancer Biology

In the early days of marker development, it was assumed that we could subset patients for counseling and treatment on the basis of marker and clinical data that predicted outcome. Unfortunately, clinical and tumor biology heterogeneity among breast cancer patients made an exact prediction of outcome for an individual patient more difficult than anticipated. While prognostic studies can provide an estimate of risk, translation to a single patient is inherently more complex. Recently reported treatment marker interactions have made prognostic marker studies even more difficult. The use of archival tumor banks, comprising heterogeneously treated patients is no longer acceptable for verification studies of prognostic markers. Increasingly, such studies are performed on patient samples derived from cooperative group-based randomized trials. This design allows testing for treatment marker interac-tions.50'51 Marker therapy interactions may be confounding. While the relationship may be...

Univariate and Multivariate Analyses

When establishing the usefulness of a breast cancer marker, it is important to perform both univariate and multivariate analyses. Univariate analysis determines whether the factor predicts the end point. It does not consider the influence of other factors and, therefore, can be misleading. In evaluating novel markers, it is often unknown whether the marker is a cause or a result of the cancerous process. Thus, associations between the presence or absence of a marker with a better or worse survival does little to advance our understanding of the underlying biology or improve predictability of outcome. Probability values (p-values) are poor indicators of relative statistical ranking of the importance of multiple factors. For example, a factor that is

Breast Preservation Therapy

Adherence to screening mammography guidelines has made most patients candidates for breast preservation therapy (BPT). Acceptance of this treatment approach has been gradual and dependent upon regional preferences and availability of radiation therapy facilities.5 When considering treatment options for early breast cancer, good cosmesis is an important goal. Improvements in surgery and radiotherapy have minimized the incidence of poor results seen initially (Figures 9-4 and 9-5). For most patients, the best cosmetic result can be achieved with breast preservation therapy and, Most randomized clinical trials included patients with T1 and T2 tumors.6-11 Thus, tumors up to 5 cm can be safely managed with this approach. A good cosmetic result may be difficult to achieve with large T2 tumors, and neoadjuvant chemotherapy may improve the ability to preserve breast tissue without compromising survival.1415 Saving the breast is important for psychological and cosmetic reasons. This requires...

Cytologic Factors and Local Recurrence

New cytologic and genetic factors are being identified and associated with breast cancer prognosis. The majority of these studies to date are small retrospective series and have not influenced the choice of therapy. Case control studies looking at the overexpression of insulin-like growth factor-I receptor (IGF-IR) and HER-2 neu indicate that overexpression may predict for an increased risk of local recurrence.70,71 In these studies, the tumor tissue of all patients who had experienced local recurrence at a single institution were evaluated for overexpression of these newly described markers. Case controls were drawn from those patients treated who did not experience local recurrence. Overexpression of IGF-IR and HER-2 neu was found significantly more frequently in patients who experienced recurrence. Although HER-2 neu overexpression negatively impacted disease-free survival in patients treated with tamoxifen and radiotherapy,72 this effect was not seen in patients treated with...

Oophorectomy and Gonadotropin Releasing Hormone Analogue

The sporadic use of adjuvant oophorectomy after breast cancer surgery in younger women was continued by surgeons for many years in the hope of preventing recurrence. Randomized trials looking at its value date back 50 years.37 Unfortunately, these early trials suffer from the lack of hormone responsiveness of most breast cancers in premenopausal women and they predate our ability to predict responsiveness with hormone receptor measurements. The EBCTCG conducted overview meta-analyses of adjuvant oophorectomy in 1985, 1990, and 1995. The most recent overview encompassed 12 trials randomizing 2,100 women to surgical or radiation oophorectomy versus no castration.38 In women under the age of 50 years, oophorectomy resulted in an 18 percent relative decrease in recurrence, an 18 percent relative decrease in death, and, at 15 years after surgery, an absolute decrease of 6.3 percent in death from any cause, compared with women not getting the procedure (p < .001).38 The relative benefit...

Magnetic Resonance Spectroscopy

Magnetic resonance spectroscopy (MRS) provides an indication of biochemical differences between tissues by its ability to measure specific metabolic products. Current experience with MRS of breast tissues principally involves pilot studies that characterize cancer-associated metabolites using 31P and 1H MR spectral profiles. While phosphate metabolites are virtually undetectable in breast fat and are identified in relatively low concentration in normal breast parenchyma, they appear to be considerably more abundant in many abnormal breast tissues, especially, in most breast cancers (Degani et al., 1986 Merchant et al., 1988 1991a 1991b Sijens et al., 1988 Twelves et al., 1994). The principal 31P MRS signals come from inorganic phosphate, phosphomonoesters, phosphocre-atine, nucleoside triphosphates (including ATP), phosphorylated glycans, and phosphodiesters. The biochemical data derived from In the earlier 31P spectroscopy studies, relatively large voxel sizes (6 to 8 cm3) were...

Postradiotherapy Angiosarcoma

The occurrence of sarcoma following radiotherapy has been well described.94,95 The widespread acceptance of breast preservation in the treatment of breast cancer may have an unforeseen secondary result an increase in the number of patients at risk for developing post irradiation sarcoma. Postradiotherapy sarcoma was defined by Cahan and colleagues in 1948 as sarcoma developing in a previously irradiated field after a latency period of several years.96 Angiosar-coma, osteosarcoma, malignant fibrous histio-cytoma, and fibrosarcoma have all been reported in the irradiated breast. Angiosarcoma has been the topic of many recent reports.97-100 The rarity of these tumors makes the true incidence of postradiotherapy angiosarcoma of the breast difficult to determine. The estimated risk of patients treated with whole breast irradiation ranges from 0.06 to 0.4 percent.97 100-102 Strobbe and colleagues, reporting on 21 patients with postradiotherapy angiosarcomas of the breast collected from the...

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