Current status of prophylactic mastectomy

The management of women at high risk for breast cancer presents a clinical dilemma to the health-care provider as well as to the woman herself. Current options include surveillance, prophylactic surgery (mastectomy and/or oophorectomy), and/or chemoprevention. Prophylactic mastectomy, including bilateral prophylactic mastectomy in high-risk women or contralateral prophylactic mastectomy in women with primary breast cancer, has been a controversial clinical option. In this review, we address the efficacy of prophylactic mastectomy in reducing the risk of breast cancer in high-risk women, the use of this procedure, surgical complications, and its psychosocial impact. The decision to undergo prophylactic mastectomy is highly personal and must be preceded by an in-depth assessment of the woman's risk of breast cancer, and a thorough discussion of the benefits of the procedure weighed against its potential surgical risks and psychological impact. It is also imperative that the woman be informed of alternative options for management, including chemoprevention, close surveillance, and prophylactic oophorectomy.     

Association of correlates of endogenous hormonal exposure with breast cancer risk in 426 families (United States)

Objective: Women with a strong family history of breast cancer are at significantly increased risk of developing the disease. There is emerging evidence that certain reproductive factors may further elevate risk in these women. We examined whether a family history of breast cancer modifies the association between correlates of endogenous hormonal exposures and breast cancer in a study of 426 families ascertained through breast cancer probands. Methods: Analyses of reproductive factors and breast cancer were performed on 395 sisters and daughters of probands, 3014 nieces and granddaughters, and 2768 marry-ins. Results: Through 226,266 person-years of follow-up since 1952, 240 women developed breast cancer. No statistically significant interactions were observed between relationship to proband and age at menarche, age at menopause, other characteristics of the menstrual cycle, parity, age at first and last birth, infertility, and total ovulatory years. Conclusions: Our findings suggest that most reproductive factors influence breast cancer risk similarly in women with and without a family history of breast cancer. Further studies are needed on individuals who are more homogeneous with regard to hereditary background. However, other options for prevention, such as prophylactic surgery or chemoprevention, may be necessary to have a substantial impact on risk reduction in women at high genetic risk.     

Prophylactic surgery for women at high risk for breast cancer

Women at high risk for the development of breast cancer have several options open to them including increased cancer surveillance, prophylactic mastectomy and/or oophorectomy, and chemoprevention. We consider high-risk women to be those with known BRCA mutations or a strong family history characterized by multiple relatives with breast cancer, early age at diagnosis, and in some families, ovarian cancer. We present existing data regarding prophylactic surgery for these women. Essentially, a woman at high risk for breast cancer may choose to undergo bilateral prophylactic mastectomy, with or without reconstruction. For patients who have a known breast cancer, contralateral mastectomy is also an option. Finally, for women in families with a strong incidence of ovarian cancer, prophylactic oophorectomy can be considered.     

Risk estimation for breast cancer development; a clinical perspective

Breast cancer is the commonest cancer among women and the second highest cause of cancer death. It remains a significant health problem and represents a significant worry for many women and their physician. During the last years, intensive research has been focused on accurate risk estimation for breast cancer development. The aim of these efforts is to identify the "high-risk" group of women for breast cancer development. Preventive strategies (including intensive surveillance, chemoprevention, or prophylactic mastectomy) may be applied for the women at high risk for breast cancer development. Given the many management options, it seems reasonable that management of the high-risk woman be tailored to the level of risk she is willing to accept. In estimating the risk for breast cancer development, several factors should be taken into account (including age, reproductive factors, such as age at menarche and age at menopause or pregnancy and age at first live birth, history of benign breast lesions or breast cancer in situ [LCIS/DCIS], prior history of breast cancer, history of familiar or hereditary breast cancer, and environmental and lifestyle factors). Recently, quantitative risk estimation is possible by combining multiple risk factors into a comprehensible risk expression; this is of significant clinical importance, since it will reduce the considerable variation in management among health care providers. The Gail and the Claus model are the most widely used models for quantitative risk estimation. However, the clinician should understand that all models have some limitations that should be recalled as they are applied. It should be emphasized that risk assessment is a serious undertaking and should only be performed by those who have in-depth knowledge about risk factors, family pedigree analysis, comparative statistics, genetics susceptibility testing and the science of probability.     

Genetic counselling and the intention to undergo prophylactic mastectomy: effects of a breast cancer risk assessment

Scientific reports suggest that women at risk for familial breast cancer may benefit from prophylactic mastectomy. However, few data are available about how women decide upon this clinical option, and in particular, what role an objective risk assessment plays in this. The purpose of the present study is to assess whether this objective risk information provided in genetic counselling affects the intention for prophylactic mastectomy. Additionally, the (mediating) effects of breast cancer worry and perceived risk are investigated. A total of 241 women completed a questionnaire before and after receiving information about their familial lifetime breast cancer risk in a genetic counselling session. Path analysis showed that the objective risk information had a corrective effect on perceived risk (beta=0.38; P=0.0001), whereas the amount of breast cancer worry was not influenced by the counselling session. The objective risk information did not directly affect the intention for prophylactic mastectomy. The intention was influenced by perceived risk after counselling (beta=0.23; P=0.002), and by the precounselling levels of perceived risk (beta=0.27; P=0.00025) and breast cancer worry (beta=0.32; P=0.0001), that is, higher levels of perceived risk and breast cancer worry imply a stronger intention for prophylactic mastectomy. A personal history of breast cancer did not directly influence the intention for prophylactic mastectomy, but affected women who had undergone a mastectomy as surgical treatment were more positively inclined to have a prophylactic mastectomy than women who had had breast-conserving therapy. The impact of objective risk information on the intention for prophylactic mastectomy is limited and is mediated by perceived risk. Important determinants of the intention for prophylactic mastectomy were precounselling levels of breast cancer worry and perceived risk, suggesting that genetic counselling is only one event in the entire process of decision making. Therefore, interventions aimed at improving decision making on prophylactic mastectomy should explicitly address precounselling factors, such as personal beliefs and the psychological impact of the family medical history.     

Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers.

BACKGROUND: In women with a family history of breast cancer, bilateral prophylactic mastectomy is associated with a decreased risk of subsequent breast cancer of approximately 90%. We examined the association between bilateral prophylactic mastectomy and breast cancer risk in women at high risk for breast cancer who also had mutations in BRCA1 and BRCA2 genes. METHODS: We obtained blood samples from 176 of the 214 high-risk women who participated in our previous retrospective cohort study of bilateral prophylactic mastectomy. We used conformation-sensitive gel electrophoresis and direct sequence analysis of the blood specimens to identify women with mutations in BRCA1 and BRCA2. The carriers' probabilities of developing breast cancer were estimated from two different penetrance models. RESULTS: We identified 26 women with an alteration in BRCA1 or BRCA2. Eighteen of the mutations were considered to be deleterious and eight to be of uncertain clinical significance. None of the 26 women has developed breast cancer after a median of 13.4 years of follow-up (range, 5.8-28.5 years). Three of the 214 women are known to have developed a breast cancer after prophylactic mastectomy. For two of these women, BRCA1 and BRCA2 screening was negative, and no blood specimen was available for the third. Estimations of the effectiveness of prophylactic mastectomy were performed, considering this woman as both a mutation carrier and a noncarrier. These calculations predicted that six to nine breast cancers should have developed among the mutation carriers, which translates into a risk reduction, after bilateral prophylactic mastectomy, of 89.5%-100% (95% confidence interval = 41.4% to 100%). CONCLUSIONS: Prophylactic mastectomy is associated with a substantial reduction in the incidence of subsequent breast cancer not only in women identified as being at high risk on the basis of a family history of breast cancer but also in known BRCA1 or BRCA2 mutation carriers.     

Breast cancer epidemiology, prevention, and early detection.

Breast cancer remains a worldwide public health concern despite the fact that mortality rates have been declining in some countries as a result of improvements in adjuvant therapy and screening for breast cancer. In the prevention arena, advances in our understanding of the effects of tamoxifen have led to the investigations of newer agents that may provide extended options for breast cancer prevention in high-risk women. For women who are carriers of a mutation in the breast cancer susceptibility genes BRCA1 or BRCA2, prophylactic oophorectomy and bilateral mastectomy have emerged as preventative surgical options that can significantly impact breast cancer risk. In addition, the identification of potentially modifiable risk factors for breast cancer such as dietary folate intake, alcohol consumption, physical activity, and certain anthropometric factors provides opportunities for intervening in breast cancer prevention both among women at average and high risk. The challenge remains in overcoming the limitations of mammography and clinical breast examination by developing and evaluating new technologies for breast cancer screening such as digital mammogram and breast magnetic resonance imaging.     

乳腺癌高危妇女的评估与预防策略

乳腺癌是女性最常见的恶性肿瘤之一。流行病学研究发现乳腺癌有许多高危因素,其中最主要的因素包括年龄、乳腺癌家庭史和既往某些乳腺疾病史。对于乳腺癌的高危人群开展预防工作是目前的一项重要课题,常用的方法包括预防性乳腺切除术、严密监测和化学预防。多项研究表明预防性乳腺切除术不能百分之百起到预防效果;乳房切除容易给妇女带来严重的精神创伤,因而必须严格掌握手术指证,术后也宜首选即刻乳房重建。严密监测应包括定期     

The management of women at high risk for the development of breast cancer: risk estimation and preventative strategies

Despite recent progress in the diagnostic and therapeutic approaches to the management of women with breast cancer, at least one third of these women will ultimately die from their disease. This resulted in a new focus on breast cancer prevention, especially for the woman designed as "high-risk". The continuing challenge is to identify reliable markers to accurately recognize this group of women, who are more likely to develop breast cancer. This will allow a targeted specific counseling and the application of preventative measures. Management options in high-risk women include intensive cancer surveillance, chemoprevention (mainly using tamoxifen), and prophylactic surgery (preferentially total mastectomy). Cancer surveillance is the most preferred management option. Currently, no data exists comparing prophylactic mastectomy vs. surveillance vs. chemoprevention. Thus, despite significant advances in our understanding of the biology of breast cancer, many questions remain unanswered concerning the optimal management of the high-risk woman. Patient counseling has a central role in the decision-making process and should be based on a multidisciplinary approach. The individual woman will make the final decision based on the amount of risk she is willing to accept. It is hoped that other preventative methods, such as gene therapy based on an accurate identification of specific genetic changes, will be developed in the future.     

Clinical and histological predictors of contralateral breast cancer

AIMS: Women previously treated for primary operable breast cancer are at increased risk of developing cancer in the contralateral breast. The purpose of this study was to assess the annual incidence of metachronous contralateral breast cancer (CBC) and to identify factors that predict for its development. METHODS: A retrospective study was performed on 3211 women aged 相似文献   

Risk-reduction mastectomy: clinical issues and research needs

Risk-reduction mastectomy (RRM), also known as bilateral prophylactic mastectomy, is a controversial clinical option for women who are at increased risk of breast cancer. High-risk women, including women with a strong family history of breast cancer and BRCA1/2 mutation carriers, have several clinical options: risk-reduction surgery (bilateral mastectomy and bilateral oophorectomy), surveillance (mammography, clinical breast examination, and breast self-examination), and chemoprevention (tamoxifen). We review research in a number of areas central to our understanding of RRM, including recent data on 1) the effectiveness of RRM in reducing breast cancer risk, 2) the perception of RRM among women at increased risk and health-care providers, 3) the decision-making process for follow-up care of women at high risk, and 4) satisfaction and psychological status after surgery. We suggest areas of future research to better guide high-risk women and their health-care providers in the decision-making process.     

Intention to undergo prophylactic bilateral mastectomy in women at increased risk of developing hereditary breast cancer.

PURPOSE: To assess intention to undergo prophylactic bilateral mastectomy and psychologic determinants in unaffected women at increased risk of developing hereditary breast cancer. PATIENTS AND METHODS: Three hundred thirty-three women who were awaiting their initial appointments for risk assessment, advice about surveillance, and prophylactic options at one of 14 familial cancer clinics participated in a cross-sectional, questionnaire-based survey. RESULTS: Nineteen percent of women would consider and 47% would not consider a prophylactic mastectomy, should genetic testing identify a mutation in a breast cancer-predisposing gene, whereas 34% were unsure and 1% had already undergone a prophylactic mastectomy. In a bivariate analysis, women at a moderately increased risk of developing breast cancer had the highest proportion of subjects reporting that they would consider a prophylactic mastectomy (25%), compared with women at high risk (16%) (chi(2) = 7.79; P =.051). In multivariate analyses, consideration of prophylactic mastectomy strongly correlated with high levels of breast cancer anxiety (odds ratio [OR] = 17.4; 95% confidence interval [CI], 4.35 to 69.71; P =. 0001) and overestimation of one's breast cancer risk (OR = 3.01; 95% CI, 1.43 to 6.32; P =.0036), whereas there was no association with objective breast cancer risk (P =.60). CONCLUSION: A significant proportion of women at increased risk of developing hereditary breast cancer would consider prophylactic mastectomy. Although prophylactic mastectomy may be appropriate in women at high risk of developing breast cancer, it is perhaps less so in those who have a moderately increased risk. Such moderate-risk women are likely to benefit from interventions aimed at reducing breast cancer anxiety and correcting exaggerated breast cancer risk perceptions.     

High prevalence of premalignant lesions in prophylactically removed breasts from women at hereditary risk for breast cancer.

PURPOSE: Women with a hereditary predisposition for breast cancer have an extremely high risk of developing invasive breast carcinoma, and many women consider prophylactic mastectomy to avoid this risk. The use of prophylactic mastectomy is still debated. Identification of frequent premalignant lesions in mastectomy specimens would support the preventive concept of prophylactic mastectomy. PATIENTS AND METHODS: We performed a prospective study of breast specimens from 67 women at extremely high genetic risk of breast cancer, with or without previous breast cancer, who were undergoing prophylactic mastectomy (66% were carriers of a BRCA1 or BRCA2 mutation). Breast specimens were studied by radiographic and macroscopic examination of 5-mm tissue slices, with subsequent histology of suspicious lesions and random samples from each quadrant of the breast and the nipple area. RESULTS: In 57% of the women, one or more different types of high-risk histopathologic lesions were present: 37% atypical lobular hyperplasia, 39% atypical ductal hyperplasia, 25% lobular carcinoma-in-situ, and 15% ductal carcinoma-in-situ. A 4-mm invasive ductal carcinoma was found in one woman with ductal carcinoma-in-situ. None of these lesions was detected at palpation or mammography, which were performed before the mastectomy. The presence of high-risk lesions was independently related to age older than 40 years (odds ratio, 6.6; P =.01) and to bilateral oophorectomy before prophylactic mastectomy (odds ratio, 0.2; P = 0.02). CONCLUSION: Many women at high risk of hereditary breast cancer develop high-risk histopathologic lesions, especially after the age of 40 years. Surveillance does not detect such high-risk histopathologic lesions.     

Skin-sparing mastectomy and immediate breast reconstruction

Skin-sparing mastectomy is a new surgical approach that allows a mastectomy while preserving the natural envelope of the breast. Skin-sparing mastectomy followed by immediate reconstruction can be used for prophylaxis for high- risk patients or BRCA carriers. It represents an effective treatment option for patients with extensive DCIS or early invasive breast cancer, but is contraindicated for inflammatory breast cancer and extensive skin involvement by the tumor. Skin-sparing mastectomy had similar surgical outcomes compared to non- skin- sparing mastectomy, but skin flap ischemia and necrosis is more common and is associated with a range of risk factors, including smoking. Skin-sparing mastectomy seems to be an oncologically safe technique and does not increase in particular the risk of local, regional or systemic recurrences. It facilitates immediate breast reconstruction using implants or myocutaneous flaps, resulting in excellent cosmesis and high level of patient satisfaction. This article reviews the published data on skin-sparing mastectomy and immediate reconstruction and aim to establish its current role in clinical practice, as there is a lack of prospective data.     

Factors associated with perceived risk of breast cancer among women attending a screening program

Summary A person's perception of the risk of, or susceptibility to, developing a disease is believed to be an important determinant of health-related behavior, yet little is known about the determinants of perceived risk. Knowledge of these correlates may be useful in identifying and addressing barriers to performance of health behaviors such as mammography screening. Data collected from over 36,000 women participating in a breast cancer screening program in Texas were used to examine the associations between perceived risk of ever getting breast cancer and a number of demographic factors, health-related behaviors, and risk factors for breast cancer. There was a strong positive association between family history of breast cancer and risk perception (OR=11.3, CI=10.34–12.35). Women who reported other risk factors for breast cancer also reported higher perceived risk, but those associations were of lesser magnitude. Age was inversely associated with perceived risk, and black, but not Hispanic, women were more likely to perceive their risk as high compared with white women. Of the health-related behaviors for the early detection of breast cancer, only having had a prior mammogram was associated with perceived risk. Educational interventions to heighten women's awareness of breast cancer risk factors may increase perceived risk in high risk women and influence their decision to undergo screening mammography.     

Surgical decisions made by 158 women with hereditary breast cancer aged <50 years

AIM: To establish the uptake of contralateral risk reducing mastectomy in women informed of their risks and options at time of diagnosis of their primary unilateral breast cancer. METHODS: We have assessed the surgical choices of 70 women diagnosed with breast cancer <50 years as part of a family history surveillance program and fully informed about their contralateral risks and surgical options. We have compared this to women from other surgical clinics who were subsequently found to harbour a pathogenic BRCA1/2 mutation. RESULTS: Sixty-five percent (13/20) of BRCA1/2 mutation carriers and 59% (n=20/34) of those at the highest level of risk pre-diagnosis (33+% lifetime risk) opted for contra-lateral mastectomy in the study sample. In contrast only 10% (n=9/88) women identified as mutation carriers from other clinics opted for such surgery. CONCLUSIONS: We would suggest that women with a significant family history and therefore a high contra-lateral breast cancer risk, should have these risks and management options discussed at the time of diagnosis of breast cancer.     

Breast reconstruction: àla carte not table d'hote

NICE guidelines emphasise the need for breast cancer patients undergoing mastectomy to be offered all appropriate options for immediate reconstruction. In the majority of hospitals this is not happening. Patients are being offered the reconstruction technique for which their surgeon has been trained and many never meet an oncoplastic surgeon to discuss the wide range of options that are available. This means that many have sub-optimal reconstructions often using implants that may need to be subsequently replaced and are incompatible with post-operative radiotherapy. Patients will be better served by a few high throughput, high quality centres specialising in tailoring the right reconstruction for the woman who needs a mastectomy rather than the present system of having reconstruction of variable quality available ubiquitously.     

Recommendations for women with lobular carcinoma in situ (LCIS)

Atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) represent a spectrum of breast disease referred to as "lobular neoplasia" (LN). Although LN occurs relatively infrequently, it is associated with an increased risk of breast cancer, ranging from a three- to four-fold increased risk with ALH up to an eight- to ten-fold increased risk with LCIS. Initially regarded as a direct precursor to invasive lobular carcinoma, LCIS used to be treated by mastectomy. Subsequent studies demonstrating that the risk of invasive disease was conferred bilaterally and that subsequent cancers were of both the ductal and lobular phenotype led to the acceptance of LCIS as a marker of increased risk rather than a true precursor. Today, a diagnosis of LCIS remains one of the greatest identifiable risk factors for the subsequent development of breast cancer. As such, patients are offered one of three options: (1) lifelong surveillance with the goal of detecting subsequent malignancy at an early stage; (2) chemoprevention; or (3) bilateral prophylactic mastectomy. Paralleling changes in the management of invasive breast cancer, trends in the management of LCIS have moved toward more conservative management. However, we have made little progress in understanding the biology of LCIS and therefore remain unable to truly optimize recommendations for individual patients.     

Psychological adjustment among male partners in response to women's breast/ovarian cancer risk: a theoretical review of the literature

Objective: For women at high risk of developing hereditary breast and/or ovarian cancer the process of undergoing genetic testing is anxiety provoking and stressful, entailing difficult and complex decisions. Partners of high‐risk women are frequently perceived by the women as a source of support during this challenging time. Utilising Self Regulatory Theory, this paper provides a theoretically guided overview of existing data to delineate how partners respond emotionally and behaviourally to the woman's high‐risk status. Methods: An extensive literature search was undertaken. Online searches of MEDLINE, CINAHL and PsycINFO databases were conducted, reference lists of all publications identified were examined; and the databases were searched for authors identified in these publications. Results: The systematic search yielded 10 published studies on at‐risk women and their male partners; one study did not investigate male partner distress as an outcome variable. Heterogeneity of methodology in this literature precluded quantitative meta‐analyses of study outcomes. Review of the evidence suggests that the genetic testing process may be distressing for some partners, particularly for partners of women identified as mutation carriers. Associations were identified between partner distress and partner beliefs about the woman's perceived breast cancer risk; partner feelings of social separation and lack of couple communication; and partner perceptions of being alienated from the testing process. Lack of partner support was found to be associated with increased distress of the tested woman at the time of testing and following results disclosure. Data are lacking on the role of partner beliefs about breast cancer, partner perceived consequences of genetic testing, and personality factors such as information processing style, on partner distress. Conclusions: The high level of behavioural and psychological interdependence that exists between a tested woman and her partner means that future research seeking to understand the coping and adjustment processes of partners needs to adopt a dyadic, transactional approach that is grounded in psychological theory. Specific suggestions for future research in this context are delineated. Copyright © 2009 John Wiley & Sons, Ltd.     

Advising women at high risk of breast cancer

Women with any family history of breast cancer assume a high probability of risk. Counseling women involves ascertainment of an accurate family history and use of the best predictive models to assess both the risk of a known mutation and the risk of breast cancer. This risk must then be considered in the contexts of both the women's lifetime and the next decade, in each instance carefully separating the risk of developing cancer from the risk of mortality. These two risks are often emotionally melded in women who have watched a loved one die of cancer. The options for a woman at significantly increased risk of breast cancer include optimal surveillance, chemoprevention, and prophylactic surgery. This entire field is in continuing evolution as better methods of diagnosis, screening, and chemoprevention continue to enter clinical practice.