Johnson, Joanne L.

PURPOSE: To estimate the efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer. PATIENTS AND METHODS: We followed the course of 745 women with a first breast cancer and a family history of breast and/or ovarian cancer who underwent contralateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. Family history information and cancer follow-up information were obtained from the medical record, a study-specific questionnaire, and telephone follow-up. Life-tables for contralateral breast cancers, which consider age at first breast cancer, current age, and type of family history, were used to calculate the number of breast cancers expected in our cohort had they not had a prophylactic mastectomy. RESULTS: Of the 745 women in our cohort, 388 were premenopausal (age < 50 years) and 357 were post- menopausal. Eight women developed a contralateral breast cancer. Six events were observed among the premenopausal women, compared with 106.2 predicted, resulting in a risk reduction of 94.4% (95% confidence interval [CI], 87.7% to 97.9%). For the 357 postmenopausal women, 50.3 contralateral breast cancers were predicted, whereas only two were observed, representing a 96.0% risk reduction (95% CI, 85.6% to 99.5%). CONCLUSION: The incidence of contralateral breast cancer seems to be reduced significantly after contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.

Abstract Introduction: Current models to predict breast cancer risk do not differentiate risk for estrogen receptor (ER) positive and negative breast cancer (BC), despite growing evidence that these tumors are biologically very different. We hypothesized that women with ER+ BC cancers have different clinical risk factors and histologic findings on prior benign breast biopsies than those with ER- BC. Methods: After IRB approval, we examined associations of age at benign biopsy and histologic features of the benign biopsy with ER status of incident BCs within the Mayo Benign Breast Disease Cohort. Benign biopsy slides were reviewed for extent of lobular involution and degree of epithelial proliferation by a single breast pathologist blinded to BC events. Invasive BCs occurring within 15 years after benign biopsy were classified as ER+ if ER staining was &gt;1%. BC case-only associations with ER status were evaluated using multivariate logistic regression. Full-cohort hazard ratios (HR) and 95% confidence intervals (CI) for risk of ER-specific subtypes were estimated using Cox proportion hazards regression. Results: Among 13,410 women undergoing a benign breast biopsy from 1967-2001, 656 invasive BCs (459 ER+, 106 ER, 106 unknown) occurred within 15 years. Women who developed ER+ and ER- BCs were similar in age at the time of their prior benign breast biopsy (p=0.34). Although benign biopsies in women who later developed ER+ BC were more likely to show complete involution (23% vs 15% for ER- BC), this was not statistically significant (p=0.06). However, the degree of epithelial proliferation was significantly associated with ER status of later BCs (p=0.001), with ER+ BCs more likely than ER- BCs to have had a prior biopsy with atypical hyperplasia (16% vs 8%), and ER+ BCs less likely than ER- BCs to have had a prior biopsy with proliferative disease without atypia (33% vs 52%); this association remained after multivariate adjustment (p=0.003). We further pursued the association of epithelial proliferation with differential risk of ER+ and ER- BC in our overall cohort of 13,410 women (Table 1). Compared to women with non-proliferative disease, women with proliferative disease +/- atypia had ∼2-fold hazard ratios for ER- BC, whereas hazard ratios for ER+ BC were higher in women with atypical hyperplasia (∼4-fold) compared to proliferative disease. Hazard Ratio of ER+ and ER- BC within 15 years of BBD based upon degree of epithelial proliferation at benign biopsyCancer TypeGroupNN EventsHazard Ratio (95% CI)p-valueInvasive ER- ≤15 yearsNP8478421.00 (ref)&lt;0.0001 PD4229542.63 (1.76, 3.93) AH70382.60 (1.22, 5.54) Invasive ER+ ≤15 yearsNP84782321.00 (ref)&lt;0.0001 PD42291511.33 (1.09, 1.64) AH703744.41 (3.39, 5.73) NP=nonproliferative disease, PD=proliferative disease without atypia; AH=atypical hyperplasia Conclusion: ER+ and ER- breast cancers appear to have different features on prior benign breast biopsy, with atypical hyperplasia showing increased risk for both types of breast cancer, but a greater risk for ER+ tumors. Citation Format: Amy C Degnim, Derek C Radisky, Robert A Vierkant, Ryan D Frank, Marlene H Frost, Vernon S Pankratz, Celine M Vachon, Tanya L Hoskin, Julie M Cunningham, Chen Wang, Jean-Pierre Kocher, Teresa M Allers, Joanne L Johnson, Tina J Hieken, Karthik Ghosh, Lynn C Hartmann, Daniel W Visscher. Histologic features of benign breast biopsy tissue and association with ER positive and ER negative breast cancer in the Mayo BBD cohort study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-10-06.

Abstract Objective: Contralateral PM (CPM) and Bilateral PM (BPM) markedly decrease, but do not completely eliminate the possibility of development of a new BC on the side of the PM. Given the relative infrequency of its occurrence, little is known about the clinical characteristics, presentation, and management of patients who develop BC after PM. Our aim was to review our institutional experience of BC occurring after PM. Methods: Between 1960 and 1993, 1,065 women underwent BPM and 1,643 women with unilateral BC treated with therapeutic mastectomy underwent a CPM. Medical records were reviewed and study-specific questionnaires were sent to all women at 10 years and 20 years after PM. BC after PM included locoregional invasive BC or DCIS on the side of the PM. Results: Thirteen patients who underwent BPM developed BC after PM. Twelve patients who underwent CPM developed a subsequent BC on the side of the CPM. The median follow-up time from PM was 22 years (range 3-34). Detailed clinical characteristics of BC after PM are shown in Table 1. Presentations included: disease limited to the axilla without evidence of a local primary 4 (16%); synchronous local and axillary disease 1 (4%); synchronous local disease and distant metastases 4 (16%); clinically isolated local disease 17 (68%). Characteristics of BC Following PM All Patients (n=25)BPM Cohort (n=13)CPM Cohort (n=12)Median age at diagnosis of BC after PM56 (range 38-81)58 (range 38-71)54 (range 39-81)Median time to development of BC after PM (years)7 (range 1-25)6 (range 2-25)8 (range 1-21)Presentation Self-detected abnormality23 (92%)12 (92%)11 (92%)Screening mammogram1 (4%)02 (16%)Not known1 (4%)1 (8%)0Local disease only17 (68%)10 (77%)7 (58%)-Sub-areolar7 (41%)6 (40%)1 (8%)-UOQ/axillary tail2 (12%)02 (16%)-Lower/inframmamary crease2 (12%)1 (10%)1(8%)Chest wall or unspecified6 (35%)3 (30%)3 (25%)Local & regional (axillary) disease1 (4%01 (8%)Axillary BC without evidence of local primary4 (16%)1 (8%)3 (25%)Synchronous local and distant disease3 (12%)2 (15%)1 (8%) Of the 17 patients with isolated local disease, 11 (65%) underwent a completion/redo mastectomy, local excision of the tumor was performed in 5 (29%), and surgical management was unknown in 1 (6%). Ten of 17 (59%) underwent axillary lymph node dissection, 1 (6%) underwent sentinel lymph node biopsy, 1 did not undergo axillary staging, and axillary management was unknown in 5 (29%). Median tumor size was 0.9 cm (range 0.3-3.5) and only 1 of 17 (6%) patients was confirmed to have pathologic nodal involvement. Twelve of 17 (71%) received some type of adjuvant therapy: chemotherapy and/or endocrine therapy 3 (18%); radiotherapy 2 (12%); both 5 (29%); none 5 (29%). With a median follow-up of 7 years since diagnosis of local BC after PM, there has been one isolated local recurrence and 2 distant recurrences as first event. Conclusion: BC can occur after PM. With rising rates of PM, understanding management of BC after PM is important. Most common presentation is local disease and can be managed with resection with consideration of adjuvant therapy. Multidisciplinary management of these cases is needed. Citation Format: Robert W Mutter, Tanya L Hoskin, Marlene H Frost, Joanne L Johnson, Lynn C Hartmann, Judy C Boughey. Breast cancer (BC) following prophylactic mastectomy (PM), a clinical entity: Presentation, management, and outcomes [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-12-05.

Purpose Contralateral prophylactic mastectomy (CPM) is one option for reducing the risk of a second breast cancer in women with a personal and family history of breast cancer. Few data are available regarding satisfaction, psychological, and social function after CPM. The purpose of this research is to evaluate women’s long-term satisfaction with CPM, factors influencing satisfaction, and psychological and social function after CPM. Patients and Methods This was a descriptive study of all women with a family history of breast cancer, known to be alive, who elected CPM at Mayo Clinic (Rochester, MN) between 1960 and 1993 (n = 621). Ninety-four percent of the women (n = 583) completed a study-specific questionnaire. Results A mean of 10.3 years after the procedure, the majority of women (83%) were satisfied with their CPM. A smaller number were neutral (8%) or dissatisfied (9%). Women who had a subcutaneous mastectomy had more problems with reconstruction, and fewer of these women were satisfied than women with simple mastectomy. Decreased satisfaction with CPM was associated with decreased satisfaction with appearance, complications with reconstruction, reconstruction after CPM, and increased level of stress in life. The majority of women experienced no change or favorable effects in self-esteem (83%), level of stress in life (83%), and emotional stability (88%). Satisfaction with body appearance, feelings of femininity, and sexual relationships were the most adversely affected with 33%, 26%, and 23% of the women responding negatively. Conclusion Although most women are satisfied with CPM, each woman should weigh the benefits alongside the potential adverse effects.