Citations

Abstract Although the association between benign breast disease (BBD) and risk of subsequent breast cancer is well-established, no previous studies have compared characteristics of breast cancers in women with a history of BBD to characteristics of cancers in the general population. In this study, we compared the characteristics of 109 breast cancers that developed in a population of African-American women with a history of benign breast disease (BBD population) to 10,601 breast cancers that developed in a general population of African-American women whose cancers were recorded by the Metropolitan Detroit Cancer Surveillance System (MDCSS population). The populations were compared on demographic characteristics such as age, marital status, and previous cancers, as well as clinical characteristics such as tumor hormone receptor status, grade, stage, behavior, size, and treatment. Overall and breast cancer-specific survival were also compared between populations. Women in the BBD population developed lower grade, earlier stage cancers that were more likely to be hormone receptor-positive and less likely to exhibit invasive behavior. Women in the BBD population were also significantly less likely to die from breast cancer after ten years of follow-up. These results suggest that although women with a history of BBD are at greater breast cancer risk, their breast cancers may be more likely to be detected early, leading to better breast cancer-specific survival. Citation Format: Susanna D. Mitro, Rouba Ali-Fehmi, Sudeshna Bandyopadhyay, Baraa Alosh, Bassam Albashiti, Quratulain Ahmed, Derek C. Radisky, Marlene H. Frost, Amy C. Degnim, Julie J. Ruterbusch, Michele L. Cote. Clinical characteristics of breast cancers in African American women with benign breast disease: A comparison to the Surveillance, Epidemiology and End Results Program. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B39. doi:10.1158/1538-7755.DISP13-B39

Abstract Introduction: Histologic characteristics of nonmalignant breast tissues (epithelial proliferation and involution) are associated with future breast cancer (BC) risk. We evaluated immune infiltration (lobulitis) in benign breast lobules and its association with features of BC risk. Methods: We analyzed archived nonmalignant breast tissue samples from 81 women in age-matched groups of varying cancer risk: 27 with benign breast disease (BBD) who later developed BC (cases), 27 with BBD without subsequent BC (controls), and 27 normal women without clinical breast disease from the Komen Tissue Bank at Indiana University (KTB). Up to 10 lobules in each sample were characterized by H&E for lobulitis, involution (none, partial, complete), and fibrocystic (FC) status (normal, nonproliferative, proliferative). Lobulitis was defined by H&E staining as lymphocyte nuclei in the intralobular stroma at low magnification and between adjacent acini at high magnification. Data was analyzed by mixed effects logistic regression. Results: Median age was 57 years (range 37-70). Among 81 breast tissue samples, 750 lobules were evaluated: 249 in BBD Cases, 265 in BBD Controls, and 236 in KTB donors. 56% of lobules were normal and 44% were FC, with 87% of FC lobules occurring in BBD samples. Lobulitis was present in 44% of lobules and varied according to subject age and individual lobule features. Younger women were more likely to have lobulitis (p=0.002); among women <50 the median proportion of lobules with lobulitis was 50%, versus 30% among women 50+. Lobulitis was less frequent in lobules with complete involution (37%) compared to partial (74%) or no involution (84%), p<0.0001. Lobulitis was common in normal lobules (52%) and decreased with increasing epithelial abnormality-39% of nonproliferative lobules and 27% of proliferative lobules (p<0.0001). In multivariate analysis including all 3 variables, all 3 remained significantly associated with lobulitis: age (p=0.03), proliferation (p<0.0001), and involution (p=0.0001). Lobules with lobulitis were less frequent in groups of women with increased breast cancer risk-55% of lobules in normal KTB samples, 43% in BBD controls, and 35% in BBD cases (p = 0.02). Conclusion: Lobulitis is common in normal and benign breast tissue lobules but varies with age, involution status, and epithelial abnormality. Further work is needed to understand the role of immune infiltrates in breast cancer risk. Citation Format: Rushin D. Brahmbhatt, Daniel W. Visscher, Tanya L. Hoskin, Derek C. Radisky, Linda M. Murphy, Melody L. Stallings Mann, Erin Miller, Vernon S. Pankratz, Lynn C. Hartmann, Marlene H. Frost, Amy C. Degnim. Immune infiltration of normal and benign breast lobules varies in breast tissues based on cancer risk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1652. doi:10.1158/1538-7445.AM2014-1652

Abstract Background: Mammographic breast density (MBD) reflects the proportion of fibroglandular tissue in the breast, and is an established risk factor for breast cancer. Benign breast disease (BBD) is also a known risk factor for breast cancer. We previously showed an association between lobular involution (physiologic atrophy) and MBD in a large cohort study of women with BBD. We performed a comprehensive evaluation of the association of histologic features of BBD with MBD. Methods: The Mayo BBD cohort includes women, 18 to 85 years, who were diagnosed with BBD at Mayo Clinic in Rochester, MN between 01/01/1967 and 12/31/1991. For this study, we included women who had a mammogram within 6 months of BBD diagnosis, and diagnosed with BBD between 1985 and 1991 when parenchymal pattern of breast density was clinically recorded. Risk factor information such as age, and body mass index (BMI) was collected from medical records. Parenchymal pattern, assessed clinically and previously used in multiple studies of MBD and risk, classified breast density based on extent and type of density, into four categories: N1 (non-dense, no ducts visible); P1 (ductal prominence occupying <25% breast); P2 (prominent ductal pattern occupying >25% of the breast; DY (homogenous plaque-like areas of density). All assessments of benign breast tissue were performed by expert breast pathologists blinded to both MBD and BBD reports. Histologic characteristics included overall impression (non-proliferative disease (NPD), proliferative disease without atypia (PDWA), and atypical hyperplasia (AH)), proportion of normal lobules that were involuted (no (0%), partial (1 to 74%), or complete (≥75%)), type of AH (ADH or ALH), ductal and lobular hyperplasia, calcifications, sclerosing adenosis, columnar alteration, cyst, fibroadenoma, marked fibrosis, intra-ductal papilloma, radial scar (number and size), duct ectasia, and mucocele like tumors. Associations of parenchymal pattern with BBD characteristics were examined using multicategorical nominal logistic regression models. We first examined associations after adjustment for age and BMI. All variables statistically significant (p<0.05) in these models were then simultaneously included in a fully-adjusted model. Results: Of 2,257 women in the study, 14% were <40 years old, 52.7% between 40- 59 years, and 32.9% were ≥60 years. In this sample, 55.2% of women had NPD, 36% had PDWA, and AH in 8.8%. MBD was classified as N1 in 21.8%, P1 in 12.6%, P2 in 23.7% and DY in 41.9%. Age- and BMI-adjusted analyses showed that there was an association of parenchymal pattern with overall impression, lobular involution, ductal hyperplasia, sclerosing adenosis, columnar alteration, cyst, duct ectasia and fibrosis. Multivariate analyses found that women of younger age (p<0.001) and with lower BMI (p<0.001), presence of fibrosis (p<0.001) and no involution (p=0.016) were more likely to have P2 or DY parenchymal pattern than women without those characteristics. Conclusion: Among women with benign breast disease, higher MBD is associated with younger age, lower BMI, fibrosis, and lack of lobular involution. These findings, concordant with other studies of MBD, provide insight into underlying mechanisms by which MBD and BBD contribute to breast cancer risk. Citation Format: Karthik Ghosh, Robert A Vierkant, Ryan D Frank, Daniel W Visscher, Vernon S Pankratz, Christopher G Scott, Derek C Radisky, Marlene H Frost, Lynn C Hartmann, Amy C Degnim, Celine M Vachon. Association between mammographic breast density and histologic features of benign breast disease [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 P6-10-14.

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 >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)<0.0001 PD4229542.63 (1.76, 3.93) AH70382.60 (1.22, 5.54) Invasive ER+ ≤15 yearsNP84782321.00 (ref)<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 BACKGROUND: Flat epithelial atypia (FEA) is a recently described breast lesion that may coexist with cancer or atypical ductal hyperplasia (ADH). Currently, there is no consensus on whether to surgically excise FEA diagnosed by core needle biopsy. Our aim was to perform a systematic review and meta-analysis of pertinent studies to determine the frequency of upgrade to cancer or ADH at surgical excision of "pure" FEA (no other high risk lesion on core biopsy). METHODS: A retrospective search was performed using MEDLINE, Embase, Scopus and Web of Science databases from 1/2003- 4/2014 to capture studies on core biopsy diagnosed FEA followed by surgical excision. Search terms were: FEA, flat epithelial atypia, DIN1A, columnar cell, breast diseases, core needle biopsy. Inclusion criteria were: 1) manuscript with original data on FEA diagnosed on core needle biopsy, 2) data included outcome of cancer at surgical excision, 3) English Language. RESULTS: Of 224 articles, 30 met inclusion criteria. StudyTotal Pure FEA cases%N excisedN upgraded to cancer% upgradedLim, 2006862.55120Kunju 20071485.712325Martel 20076338.124938Piubello, 20093360.62000Chivukula, 20093989.735514Senneta,20094187.83600Hayes, 200981008113Davashian, 20091210012217Tamasino, 20095444.424313Noske, 20104369.83027Lee, 20101546.77114Ingegnoli, 20101883.315320Noel, 20106232.32000Flegg, 2010NANA5240Sohn, 20113666.72428Lavoue, 20116010060813Rakha, 20112410024521Soloranzo,20113384.828414Verschuur-Maes, 20116934.824938Peres, 201212879.71021010Uzoaru, 201214565.69533Bianchi, 2012190100190189Biggar, 2012511005136Yamaguchi, 20121747.18113Polom, 20122010020210Khoumais, 201310490.4941011Villa, 201314285.212176Becker, 201330378.9239104Ceugnart, 20136382.55236Uzan, 2013351003500 Across 1420 patients with pure FEA in 30 studies, observed proportions with upgrade to cancer varied from 0-40% with a pooled estimate of 11% (95% CI: 8-15%) using a random effects model. Test for heterogeneity was statistically significant (p < 0.0001, I2 statistic=58%). After excluding 7 studies with <50% (or unreported %) of all FEA cases excised, heterogeneity decreased (p=0.07, I2=32%) and the pooled estimate of cancer upgrade was 9% (95% CI: 7-12%). For upgrade to ADH, 693 subjects with pure FEA were analyzed from 21 studies. The percent upgraded to ADH ranged from 0-60% with significant heterogeneity (p < 0.0001, I2 = 64%). Excluding 4 studies with <50% of FEA cases excised did not improve heterogeneity (p < 0.0001 and I2 = 66%). The random effects model pooled estimate of upgrade to ADH was 16% (95% CI: 11-23%) for the 21 studies and 17% (95% CI: 12-25%) for the subset of 17 studies. CONCLUSION: The pooled upgrade rate of FEA to cancer was 9-11% and upgrade to ADH was 16-17%. For patients with FEA on core needle biopsy, surgical excision should be strongly considered. Citation Format: Anatoliy V Rudin, Hoskin L Tanya, Ann M Farrell, Amy C Degnim. Flat epithelial atypia on core biopsy and upgrade to cancer: A systematic review and meta-analysis [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 P2-13-06.

Acupuncture is used to treat a variety of symptoms and conditions associated with cancer and cancer treatments. The present study was performed to evaluate the feasibility of providing acupuncture in the hospital setting for breast cancer patients and to evaluate the short-term effect of acupuncture on stress, anxiety, and pain. This was an open label study conducted at Mayo Clinic Hospital, Methodist and Saint Marys Campus, Rochester, Minnesota. A total of 20 adult breast cancer patients undergoing mastectomy and/or breast reconstruction were recruited and offered daily acupuncture intervention beginning postoperative day 1 and continuing for the duration of the hospital stay. Outcome measures included the Symptom Visual Analog Scale (VAS) and Satisfaction Question and Was-it-Worth-it (WIWI) Questionnaire. It was found that acupuncture is a feasible option for postoperative breast cancer patients. In addition, it can significantly decrease the levels of anxiety (p = 0.0065), tension/muscular discomfort (p < 0.001) and pain (p = 0.023). The association between acupuncture and relaxation was found to be statistically borderline (p = 0.053). This feasibility study showed that acupuncture can be integrated into a busy postsurgical clinical practice. These results also suggest that acupuncture may be an important intervention in the postoperative setting for breast cancer patients.

Purpose Optimal early detection and prevention for breast cancer depend on accurate identification of women at increased risk. We present a risk prediction model that incorporates histologic features of biopsy tissues from women with benign breast disease (BBD) and compare its performance to the Breast Cancer Risk Assessment Tool (BCRAT). Methods We estimated the age-specific incidence of breast cancer and death from the Mayo BBD cohort and then combined these estimates with a relative risk model derived from 377 patient cases with breast cancer and 734 matched controls sampled from the Mayo BBD cohort to develop the BBD–to–breast cancer (BBD-BC) risk assessment tool. We validated the model using an independent set of 378 patient cases with breast cancer and 728 matched controls from the Mayo BBD cohort and compared the risk predictions from our model with those from the BCRAT. Results The BBD-BC model predicts the probability of breast cancer in women with BBD using tissue-based and other risk factors. The concordance statistic from the BBD-BC model was 0.665 in the model development series and 0.629 in the validation series; these values were higher than those from the BCRAT (0.567 and 0.472, respectively). The BCRAT significantly underpredicted breast cancer risk after benign biopsy (P = .004), whereas the BBD-BC predictions were appropriately calibrated to observed cancers (P = .247). Conclusion We developed a model using both demographic and histologic features to predict breast cancer risk in women with BBD. Our model more accurately classifies a woman's breast cancer risk after a benign biopsy than the BCRAT.

BACKGROUND Based on its cytologic features, and its co‐occurrence with atypical hyperplasia and breast cancer, flat epithelial atypia (FEA) has been proposed as a precursor lesion on the pathway to the development of breast cancer. It is often referred to as an “atypical” or high‐risk lesion. However, to the authors' knowledge, the long‐term risk of breast cancer in women with FEA is undefined. METHODS Specimens with FEA were identified among excisional breast biopsies in the Mayo Clinic Benign Breast Disease Cohort, which includes 11,591 women who had benign biopsy findings at the Mayo Clinic in Rochester, Minnesota between 1967 and 2001. Breast cancer risk among subsets of patients with FEA and nonproliferative, proliferative, and atypical hyperplasia (AH) was assessed using standardized incidence ratios (SIRs) compared with the Iowa Surveillance, Epidemiology, and End Results registry. RESULTS FEA was identified in 282 women (2.4%); 130 had associated AH (46%) and 152 (54%) were classified as having proliferative disease without atypia (PDWA). With median follow‐up of 16.8 years, the SIR for breast cancer in patients with AH plus FEA was 4.74 (95% confidence interval [95% CI], 3.17‐6.81) versus 4.23 (95% CI, 3.44‐5.13) for those with AH without FEA ( P = .59). The SIR for patients with PDWA plus FEA was 2.04 (95% CI, 1.23‐3.19) versus 1.90 (95% CI, 1.72‐2.09) for patients with PDWA without FEA ( P = .76). CONCLUSIONS FEA is an uncommon finding in women with benign breast disease. FEA does not appear to convey an independent risk of breast cancer beyond that of the associated PDWA or AH. Cancer 2015;121:1548–1555 . © 2015 American Cancer Society .