Chemoprevention Uptake for Breast Cancer Risk Reduction Varies by Risk Factor.

BACKGROUND/OBJECTIVE: The efficacy of chemoprevention for breast cancer risk reduction has been demonstrated in randomized controlled trials; however, use remains low. We sought to determine whether uptake differed by risk factors, and to identify reasons for refusal and termination. METHODS: Women seen in a high-risk clinic from October 2014 to June 2017 considered eligible for chemoprevention (history of lobular carcinoma in situ, atypia, family history of breast/ovarian cancer, genetic mutation, or history of chest wall radiation) were retrospectively identified. Breast cancer risk factors were compared among those with and without chemoprevention use, and compliance was noted. RESULTS: Overall, 1506 women were identified, 24% with prior/current chemoprevention use. Women ≥ 50 years of age were more likely to use chemoprevention than women < 50 years of age (28% vs. 11%, p < 0.001). Chemoprevention use by risk factor ranged from 7 to 40%. Having multiple risk factors did not increase use. Significant variation by risk factor was present among women ≥ 50 years of age (p < 0.001), but not among women < 50 years of age (p = 0.1). Among women with a documented discussion regarding chemoprevention (575/1141), fear of adverse effects was the most common refusal reason (57/156; 36%). The majority of women (61%) who initiated chemoprevention completed 5 years. CONCLUSION: Chemoprevention use among women at increased risk for breast cancer remains low, with more frequent use among women ≥ 50 years of age. These data highlight the need for ongoing educational efforts and counseling, as the majority who begin therapy complete 5 years of use. Given the fear of adverse effects as well as low uptake, particularly among women < 50 years of age, alternative risk-reducing strategies are needed.

Indications for Contralateral Prophylactic Mastectomy: A Consensus Statement Using Modified Delphi Methodology.

OBJECTIVE: To reach a consensus about contralateral prophylactic mastectomy in unilateral breast cancer. SUMMARY BACKGROUND DATA: There has been a substantial increase in the number of North American women with unilateral breast cancer undergoing a therapeutic mastectomy and a contralateral prophylactic mastectomy (CPM) either simultaneously or sequentially. The purpose of this project was to create a nationally endorsed consensus statement for CPM in women with unilateral breast cancer using modified Delphi consensus methodology. METHODS: A nationally representative expert panel of 19 general surgeons, 2 plastic surgeons, 2 medical oncologists, 2 radiation oncologists, and 1 psychologist was invited to participate in the generation of a consensus statement. Thirty-nine statements were created in 5 topic domains: predisposing risk factors for breast cancer, tumor factors, reconstruction/symmetry issues, patient factors, and miscellaneous factors. Panelists were asked to rate statements on a 7-point Likert scale. Two electronic rounds of iterative rating and feedback were anonymously completed, followed by an in-person meeting. Consensus was reached when there was at least 80% agreement. RESULTS: Our panelists did not recommend for average risk women with unilateral breast cancer. The panel recommended CPM for women with a unilateral breast cancer and previous Mantle field radiation or a BrCa1/2 gene mutation. The panel agreed that CPM could be considered by the surgeon on an individual basis for: women with unilateral breast cancer and a genetic mutation in the CHEK2/PTEN/p53/PALB2/CDH1 gene, and in women who may have significant difficulty achieving symmetry after unilateral mastectomy. CONCLUSION: Contralateral prophylactic mastectomy is rarely recommended for women with unilateral breast cancer.

No survival improvement of contralateral prophylactic mastectomy among women with invasive lobular carcinoma.

BACKGROUND AND OBJECTIVE: The prognosis of contralateral prophylactic mastectomy (CPM) in women with breast cancer has been widely reported. Here, we evaluated the survival outcome among patients with invasive lobular carcinoma (ILC) to determine the potential benefit of CPM. METHODS: We used the Surveillance, Epidemiology, and End Results database to identify patients with ILC diagnosed between 1998 and 2010. Survival differences were compared between unilateral mastectomy and CPM. Propensity score matching and risk-stratified subgroup analyses were conducted to reduce selection bias. RESULTS: Among 10 226 patients with ILC, 21.8% women underwent CPM, and the rate of CPM nearly tripled over a 13-year period. Kaplan-Meier curves and hazard ratio (HR) of non-breast cancer-specific survival (non-BCSS) in multivariate analysis reflected a pre-existing selection bias in the present cohort. A Cox proportional hazard model confirmed that patients who received CPM had significantly better BCSS and overall survival (OS) in the prematching population (BCSS: HR = 0.90; OS: HR = 0.93). However, the survival improvement could not be achieved in the postmatching cohort. None of the defined subgroups had OS benefits when CPM was performed. CONCLUSIONS: CPM offers no survival advantage to patients with ILC. The role of CPM among ILC women should be further investigated by incorporating more objective factors.

Breast cancer prevention strategies in lobular carcinoma in situ: A decision analysis.

BACKGROUND: Women diagnosed with lobular carcinoma in situ (LCIS) have a 3-fold to 10-fold increased risk of developing invasive breast cancer. The objective of this study was to evaluate the life expectancy (LE) and differences in survival offered by active surveillance, risk-reducing chemoprevention, and bilateral prophylactic mastectomy among women with LCIS. METHODS: A Markov simulation model was constructed to determine average LE and quality-adjusted LE (QALE) gains for hypothetical cohorts of women diagnosed with LCIS at various ages under alternative risk-reduction strategies. Probabilities for invasive breast cancer, breast cancer-specific mortality, other-cause mortality and the effectiveness of preventive strategies were derived from published studies and from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. RESULTS: Assuming a breast cancer incidence from 1.02% to 1.37% per year under active surveillance, a woman aged 50 years diagnosed with LCIS would have a total LE of 32.78 years and would gain 0.13 years (1.6 months) in LE by adding chemoprevention and 0.25 years (3.0 months) in LE by adding bilateral prophylactic mastectomy. After quality adjustment, chemoprevention resulted in the greatest QALE for women ages 40 to 60 years at LCIS diagnosis, whereas surveillance remained the preferred strategy for optimizing QALE among women diagnosed at age 65 years and older. CONCLUSIONS: In this model, among women with a diagnosis of LCIS, breast cancer prevention strategies only modestly affected overall survival, whereas chemoprevention was modeled as the preferred management strategy for optimizing invasive disease-free survival while prolonging QALE form women younger than 65 years. Cancer 2017;123:2609-17. © 2017 American Cancer Society.

Variation in Breast Cancer-Risk Factor Associations by Method of Detection: Results From a Series of Case-Control Studies.

Concerns about breast cancer overdiagnosis have increased the need to understand how cancers detected through screening mammography differ from those first detected by a woman or her clinician. We investigated risk factor associations for invasive breast cancer by method of detection within a series of case-control studies (1992-2007) carried out in Wisconsin, Massachusetts, and New Hampshire (n=15,648 invasive breast cancer patients and 17,602 controls aged 40-79 years). Approximately half of case women reported that their cancer had been detected by mammographic screening and half that they or their clinician had detected it. In polytomous logistic regression models, parity and age at first birth were more strongly associated with risk of mammography-detected breast cancer than with risk of woman/clinician-detected breast cancer (P≤0.01; adjusted for mammography utilization). Among postmenopausal women, estrogen-progestin hormone use was predominantly associated with risk of woman/clinician-detected breast cancer (odds ratio (OR)=1.49, 95% confidence interval (CI): 1.29, 1.72), whereas obesity was predominantly associated with risk of mammography-detected breast cancer (OR=1.72, 95% CI: 1.54, 1.92). Among regularly screened premenopausal women, obesity was not associated with increased risk of mammography-detected breast cancer (OR=0.99, 95% CI: 0.83, 1.18), but it was associated with reduced risk of woman/clinician-detected breast cancer (OR=0.53, 95% CI: 0.43, 0.64). These findings indicate important differences in breast cancer risk factors according to method of detection.

Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial.

BACKGROUND: Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease. METHODS: Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319. FINDINGS: 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0-7·1), 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0·47, 95% CI 0·32-0·68, p<0·0001). The predicted cumulative incidence of all breast cancers after 7 years was 5·6% in the placebo group and 2·8% in the anastrozole group. 18 deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0·836). INTERPRETATION: Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer. FUNDING: Cancer Research UK, the National Health and Medical Research Council Australia, Sanofi-Aventis, and AstraZeneca.

Contralateral Prophylactic Mastectomy: Challenging Considerations for the Surgeon.

The use of both bilateral prophylactic mastectomy and contralateral prophylactic mastectomy (CPM) has increased significantly during the last decade. Various risk models have been developed to identify patients at increased risk for breast cancer. The indications for bilateral prophylactic mastectomy for patients without a diagnosis of breast cancer include high risk from mutation in BRCA or other breast cancer predisposition gene, very strong family history with no identifiable mutation, and high risk based on breast histology. Additionally, the use of CPM has more than doubled in the last decade, and this increase is noted among all stages of breast cancer, even in patients with ductal carcinoma in situ (stage 0). The risk of contralateral breast cancer often is overestimated by both patients and physicians. Nevertheless, specific risk factors are associated with an increased risk of contralateral breast cancer, including BRCA or other genetic mutation, young age at diagnosis, lobular histology, family history, and prior chest wall irradiation. Although CPM reduces the incidence of contralateral breast cancer, the effect on disease-free survival and, more importantly, overall survival is questionable and underscored by the fact that the reason most patients choose CPM is to achieve "peace of mind." Newer and effective reconstructive options have made the procedure more attractive. This panel addresses the indications and rationale for bilateral prophylactic mastectomy and CPM, the decision-making process by patients, and ethical considerations. Changes in the physician-patient relationship during the past few decades have altered the approach, and ethical considerations are paramount in addressing these issues.

Sentinel lymph node biopsy during prophylactic mastectomy: is there a role?

PURPOSE: We investigated rates of occult malignancy in the breast and sentinel lymph nodes (SLNs) in patients undergoing prophylactic mastectomy (PM) and whether routine sentinel lymph node biopsy (SLNB) is justified. METHODS: A retrospective review of our database identified patients undergoing PMs with SLNB. Descriptive statistics were utilized for data summary. A P value of <0.05 was considered significant. RESULTS: There were 384 patients during the study period who underwent 467 PMs. Of the 467 PMs, 15 (3.2%) cancers were found on final pathology. All 6 of the invasive cancers identified were T1. A total of 682 SLNs were taken for an average of 1.46 SLNs per PM. There were 5 positive SLNs (1.1%). All were in patients undergoing contralateral PM for either history of breast cancer or new diagnosis of breast cancer. Only one patient with a positive SLN was found to have an occult breast malignancy in the PM specimen. CONCLUSION: In 467 PMs performed, 15 (3.2%) occult malignancies were found in the breast and 5 (1.1%) positive SLNs were found. Based on these results, the routine use of SLNB at the time of PM is unnecessary and does not warrant the morbidity associated with this procedure.

Lower sensitivity of screening mammography after previous benign breast surgery.

Few data are available on the effect of previous benign breast surgery on screening mammography accuracy. We determined whether sensitivity of screening mammography and tumor characteristics are different for women with and without previous benign breast surgery. We included a consecutive series of 317,398 screening mammograms of women screened between 1997 and 2008. During 2-year follow-up, clinical data, breast imaging, biopsy and surgery reports were collected from women with screen-detected or interval breast cancers. Screening sensitivity, tumor biology and tumor stages were compared between 168 women with breast cancer and prior ipsilateral benign breast surgery and 2,039 women with breast cancer but without previous ipsilateral, benign breast surgery. The sensitivity of screening mammography was significantly lower for women with prior surgery [64.3% (108/168) versus 73.4% (1,496/2,039), p = 0.01]. The concomitant increased interval cancer risk remained significant after logistic regression adjustment for age and breast density (OR = 1.5, 95% CI: 1.1-2.1). Comparing screen-detected cancers in women with and without prior breast surgery, no significant differences in estrogen receptor status (p = 0.56), mitotic activity (p = 0.17), proportions of large (T2+) tumors (p = 0.6) or lymph node positive tumors (p = 0.4) were found. Also for interval cancers, no differences were found in estrogen receptor status (p = 0.41), mitotic activity (p = 0.39), proportions of large tumors (p = 0.9) and lymph node positive tumors (p = 0.5) between women with and without prior breast surgery. We conclude that sensitivity of screening mammography is significantly lower in women with previous benign breast surgery than without, but tumor characteristics are comparable both for screen detected cancers and interval cancers.

The role of chemoprevention in modifying the risk of breast cancer in women with atypical breast lesions.

Women with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and severe ADH are at increased risk of breast cancer, but a systematic quantification of this risk and the efficacy of chemoprevention in the clinical setting is still lacking. The objective of this study is to evaluate a woman's risk of breast cancer based on atypia type and to determine the effect of chemoprevention in decreasing this risk. Review of 76,333 breast pathology reports from three institutions within Partners Healthcare System, Boston, from 1987 to 2010 using natural language processing was carried out. This approach identified 2,938 women diagnosed with atypical breast lesions. The main outcome of this study is breast cancer occurrence. Of the 2,938 patients with atypical breast lesions, 1,658 were documented to have received no chemoprevention, and 184/1,658 (11.1 %) developed breast cancer at a mean follow-up of 68 months. Estimated 10-year cancer risks were 17.3 % with ADH, 20.7 % with ALH, 23.7 % with LCIS, and 26.0 % with severe ADH. In a subset of patients treated from 1999 on (the chemoprevention era), those who received no chemoprevention had an estimated 10-year breast cancer risk of 21.3 %, whereas those treated with chemoprevention had a 10-year risk of 7.5 % (p < 0.001). Chemoprevention use significantly reduced breast cancer risk for all atypia types (p < 0.05). The risk of breast cancer with atypical breast lesions is substantial. Physicians should counsel patients with ADH, ALH, LCIS, and severe ADH about the benefit of chemoprevention in decreasing their breast cancer risk.

Implementation of educational video improves patient understanding of basic breast cancer concepts in an undereducated county hospital population.

BACKGROUND: The purpose of this study was to evaluate the effect of a video on patient understanding of basic breast cancer concepts. METHODS: An 11 item tool of breast cancer concepts was devised. A previous study obtained baseline information on patient knowledge. Subsequently an 8 min video was designed to facilitate the understanding of these concepts. The next 40 consecutive patients who saw the video were then administered the same 11 item questionnaire. RESULTS: Eighty-one women agreed to participate in the study, 41 before and 40 after the implementation of the video. Fifty-one percent had less than a high school education. The group who saw the video had a higher mean number of questions correct (6.7 vs. 8.9, P = 0.0007). Interestingly 90% of all respondents correctly answered the question on the value of screening mammography, however, only 37% of these patients underwent screening mammograms. A multiple linear regression model adjusting for years of education, language, and seeing the video, revealed that having seen the video (P = 0.0029) and years of education (P = 0.0002) remained significantly associated with higher score. CONCLUSIONS: Implementation of an educational video significantly improved understanding of breast cancer concepts in an undereducated population.

Induction of tumor-specific immunity by multi-epitope rat HER2/neu-derived peptides encapsulated in LPD Nanoparticles.

The goal of study was first to design multi-epitope peptides from the rat HER2/neu (rHER2/neu) oncogene and then to evaluate the effectiveness of these peptides encapsulated in liposome-polycation-DNA(LPD) nanoparticles (NPs) for the induction of immune response in BALB/c mice. Four multi-epitope peptides derived from the rHER2/neu were designed and different groups of mice were vaccinated with free peptides or peptides encapsulated in NPs. Two of the four tested peptides (p5 and p435), as well as their combinations with the LPD NPs induced a significantly higher IFN-γ and CTLresponses in comparison with the control groups. Consequently, these responses led to lower tumor sizes and longer survival time in TUBO tumor mice model. Our results demonstrate that rHER2/neu-peptides (p5 and p435) and their encapsulation can induce an antigen-specific immunity. This study also presents the first attempt to evaluate the effectiveness of natural rHER2/neu-peptides containing CTL multi-epitope and encapsulated in LPD NPs. FROM THE CLINICAL EDITOR: This study represents the first attempt to evaluate the effectiveness of natural rHER2/neu-peptides containing CTL multi-epitope encapsulated in LPD NPs, demonstrating that rHER2/neu-peptides (p5 and p435) and their encapsulation can induce tumor antigen-specific immunity.

Prophylactic mastectomy: is it worth it?

BACKGROUND: Breast cancer is the second mortality-related cancer and the leading cause of general mortality in women aged 40-55. Prophylactic mastectomy has proved to be effective in several clinical scenarios but is still a somewhat controversial procedure. METHODS: We performed a retrospective study by reviewing the records of all patients who underwent prophylactic mastectomy in a 25-year period. We evaluated the aesthetic and long-term oncologic outcomes, complications, and patient satisfaction. RESULTS: We had 52 patients, 40 of them unilateral cases (contralateral prophylactic mastectomy) and 12 bilateral (bilateral prophylactic mastectomy) for a total of 64 mastectomized breasts. We had 1 (1.56%) case of unexpected breast cancer in the mastectomy specimens. Forty-two (65.62%) cases had a subcutaneous prophylactic mastectomy and 22 (34.37%) cases had a simple total prophylactic mastectomy. Fifty-eight (90.62%) cases underwent reconstruction with alloplastics and 6 (9.37) cases with autologous tissue of which 5 (7.81%) cases received latissimus dorsi flaps with alloplastic implants and 1 (1.56%) case had a TRAM flap. The complications included 4 (6.25%) breasts that developed capsular contracture, 2 (3.12%) cases of hematoma, and 1 (1.56%) infection. Concerning patient satisfaction, 39 (75%) patients reported being highly satisfied, 10 (19.23%) partially satisfied, and 3 (5.76%) unsatisfied. When we performed the aesthetic evaluation according to our scale, we got an overall aesthetic index of 8.8. CONCLUSION: Prophylactic mastectomy is becoming an increasingly frequent procedure. Plastic surgeons should consider the aesthetic outcome when planning mastectomy and reconstruction. Our ability to predict the high-risk population has improved and it is that population who can get the best benefit from this intervention. The recommendation against subcutaneous prophylactic mastectomy lacks scientific evidence. There is plenty of evidence that prophylactic mastectomy lowers the risk of breast cancer in the high-risk population in at least 95%. Our experience with prophylactic mastectomy is extremely satisfactory, with an overall patient satisfaction rate of 94%, no mortality, and an oncologic long-term outcome of 0% of ulterior development of breast cancer. Our series, although relatively small, should provide some insight into the power of this technique and we think all plastic surgeons should have it in their surgical armamentarium and should share their experiences so that this procedure may become more widely accepted. We also think that plastic surgeons should strive for perfecting the technique to reduce the complication rate and therefore help the procedure gain acceptance by the medical community.

Mastectomy and contralateral prophylactic mastectomy rates: an institutional review.

BACKGROUND: Breast conservation surgery (BCS) followed by radiation is as effective as mastectomy for long-term survival and is considered standard of care for early-stage breast cancer. An increasing number of patients are opting for cancer-side mastectomies (CM) and often contralateral prophylactic mastectomies (CPM). Our study investigates if there are increasing trends in our patient population toward CM and CPM and identifies common factors associated with those electing to have more extensive surgery. METHODS: A retrospective analysis was performed on 812 breast cancer surgeries between January 2001 and December 2009 at The George Washington University Breast Care Center. BCS-eligible patients who elected to have BCS were compared with those who chose CM. Patients who underwent CM were compared with patients undergoing CM and CPM. RESULTS: A personal or family history of breast cancer and larger tumor size were positively associated with choosing CM in BCS-eligible patients. A nonstatistically significant trend toward CM was seen in younger patients. Age, family history, fewer children, Caucasian race, and reconstructive surgery were positively associated with choosing CPM. CONCLUSION: Mastectomy rates at this institution have not shown the recent sharp increase observed by some authors. The association of age, race, family history, and parity with CPM has been corroborated in multiple studies. However, there is disagreement between statistically significant findings among investigators evaluating factors associated with CPM, and there is limited data in the literature characterizing BCS-eligible patients who chose CM. Larger prospective studies are necessary to further evaluate CM and CPM rates.

Areola and nipple-areola-sparing mastectomy for breast cancer treatment and risk reduction: report of an initial experience in a community hospital setting.

BACKGROUND: The use of areola-sparing (AS) or nipple-areola-sparing (NAS) mastectomy for the treatment or risk reduction of breast cancer has been the subject of increasing dialogue in the surgical literature over the past decade. We report the initial experience of a large community hospital with AS and NAS mastectomies for both breast cancer treatment and risk reduction. METHODS: A retrospective chart review was performed of patients undergoing either AS or NAS mastectomies from November 2004 through September 2009. Data collected included patient sex, age, family history, cancer type and stage, operative surgical details, complications, adjuvant therapies, and follow-up. RESULTS: Forty-three patients underwent 60 AS and NAS mastectomies. Forty-two patients were female and one was male. The average age was 48.7 years (range, 28-76 years). Forty mastectomies were for breast cancer treatment, and 20 were prophylactic mastectomies. The types of cancers treated were as follows: invasive ductal (n = 19), invasive lobular (n = 5), ductal carcinoma-in situ (n = 15), and malignant phyllodes (n = 1). Forty-seven mastectomies (78.3%) were performed by inframammary incisions. All patients underwent immediate reconstruction with either tissue expanders or permanent implants. There was a 5.0% incidence of full-thickness skin, areola, or nipple tissue loss. The average follow-up of the series was 18.5 months (range, 6-62 months). One patient developed Paget's disease of the areola 34 months after an AS mastectomy (recurrence rate, 2.3%). There were no other instances of local recurrence. CONCLUSIONS: AS and NAS mastectomies can be safely performed in the community hospital setting with low complication rates and good short-term results.

Perioperative complications of breast cancer surgery in elderly women (≥80 years).

PURPOSE: There has been much controversy regarding the optimal management of breast cancer in very elderly women. Some clinicians are reluctant to offer surgical treatment for women older than aged 80 years because of the assumed higher operative risk associated with advanced age. This study was designed to investigate the perioperative complications of breast cancer surgery in women of this age group. METHODS: Data were reviewed of all women ≥80 years of age who underwent breast cancer surgery at a university clinic during the period 1990-2005. Symptoms, comorbidities, preoperative risk assessment, type of operation, postoperative histological diagnosis, hospital stay, morbidity, and mortality were documented and analyzed. RESULTS: During this 16-year period, 140 operations for breast cancer were performed in 129 women. The majority of the patients (37.9%) underwent a modified radical mastectomy, 32.1% underwent a simple mastectomy, 24.3% underwent breast-conserving therapy, and 5.7% underwent an axillary lymph node dissection. Complications occurred in 37.1% of the cohort: 31.4% were minor complications and only 5.7% were major. Intraoperative morbidity was 18.6% and postoperative morbidity was 20%. Late complications occurred in 5% of patients. The most common complications were associated with the wound region (50%). The perioperative mortality in this group of elderly women was zero. CONCLUSIONS: Breast cancer surgery has acceptable perioperative morbidity and mortality in women aged ≥80 years. Surgery is the cornerstone of breast cancer treatment and should be offered as first-line treatment for all patients regardless of their age.

Perceptions of contralateral breast cancer: an overestimation of risk.

INTRODUCTION: The rate of contralateral prophylactic mastectomy (CPM) has recently increased. The aim of this study is to assess perceptions of contralateral breast cancer (CBC) risk among breast cancer patients and to evaluate tumor and patient factors associated with risk perception. METHODS: We conducted a prospective survey study to evaluate perceptions of CBC risk in women newly diagnosed with ductal carcinoma in situ (DCIS) or stage I/II invasive breast cancer. Surveys were distributed in clinic prior to surgical consultation. Exclusion criteria included history of breast cancer, bilateral breast cancer, neoadjuvant chemotherapy or radiation for the current breast cancer, or BRCA mutation. Survey questions used open-ended responses or five-point Likert scale scoring (5 = very likely, 1 = not at all likely). RESULTS: Seventy-four women (mean age 54.5 years) completed the survey. Diagnoses included invasive ductal cancer (66.2%), invasive lobular cancer (9.5%), and DCIS (20.3%). Most women (54.1%) underwent breast-conserving surgery; the remaining had bilateral mastectomy including CPM (17.6%) or unilateral mastectomy (10.8%). Overall, women substantially overestimated their risk of developing CBC. The mean estimated 10-year risk of CBC was 31.4% [95% confidence interval (CI) 24.7-37.9%] and 2.6 ± 0.15 on the rank scale. The perceived risk of CBC was not significantly associated with cancer stage, family history, age, or CPM. CONCLUSIONS: At time of surgical evaluation, women with unilateral breast cancer substantially overestimated their risk of CBC; however, this elevated risk perception was not associated with choosing CPM. Early physician counseling is needed to provide women with accurate information regarding their true CBC risk.

Contralateral prophylactic mastectomy.

BACKGROUND: Contralateral prophylactic mastectomy (CPM) is often discussed as a treatment option for women with a diagnosis of unilateral breast cancer. The purpose of this study was to identify the prevalence of pathology within the specimen at the time of CPM and to evaluate potential risk factors. METHODS: Patients with a unilateral breast malignancy who underwent CPM were identified from the database of Scott and White Breast Cancer Clinic. A retrospective cohort study comparing disease status and various exposure parameters was conducted via chart review. RESULTS: Of the 301 patients who met the inclusion criteria, there were 14 cases (4.7%) with malignancy and 45 cases (15.0%) with moderate-to-high risk lesions. Multivariate analysis demonstrated 2 independent factors predictive of malignant or moderate-to-high risk lesions: age >54 years and lobular histology in the original specimen. CONCLUSIONS: The prevalence of malignant and premalignant lesions at the time of CPM was nearly 1 in 5.

Interleukin 12-mediated prevention of spontaneous mammary adenocarcinomas in two lines of Her-2/neu transgenic mice.

The ability of interleukin (IL)-12 to prevent tumors when administered to individuals with a genetic risk of cancer was studied in two lines of transgenic mice expressing rat HER-2/neu oncogene in the mammary gland. Female BALB/c (H-2(d)) mice carrying the activated HER-2/ neu oncogene show no morphological abnormalities of the mammary gland until 3 wk of age. They then progress through atypical hyperplasia to in situ lobular carcinoma and at 33 wk of age all 10 mammary glands display invasive carcinomas. Adult FVB mice (H-2(q)) carrying the HER-2/neu protooncogene develop mammary carcinomas with a longer latency (38-49 wk) and a lower multiplicity (mean of 2.6 tumors/mice). Treatment with IL-12 (5 daily intraperitoneal injections, 1 wk on, 3 wk off; the first course with 50 ng IL-12/day, the second with 100 ng IL-12/day) begun at 2 wk of age in BALB/c mice and at 21 wk of age in FVB mice markedly delayed tumor onset and reduced tumor multiplicity. Analogous results were obtained in immunocompetent and permanently CD8(+) T lymphocyte-depleted mice. In both transgenic lines, tumor inhibition was associated with mammary infiltration of reactive cells, production of cytokines and inducible nitric oxide synthase, and reduction in microvessel number, in combination with a high degree of hemorrhagic necrosis.