A Randomized Trial of Calcium Plus Vitamin D Supplementation and Risk of Ductal Carcinoma In Situ of the Breast.

Background: The effect of calcium plus vitamin D (CaD) supplementation on risk of ductal carcinoma in situ (DCIS) of the breast, a nonobligate precursor of invasive ductal carcinoma, is not well understood. In this secondary analysis, we examined this association in the Women's Health Initiative CaD trial over approximately 20 years of follow-up. Methods: A total of 36 282 cancer-free postmenopausal women (50-79 years) were randomly assigned to daily (d) calcium (1000 mg) plus vitamin D (400 IU) supplementation or to a placebo. Personal supplementation with vitamin D (≤600 IU/d, subsequently raised to 1000 IU/d) and calcium (≤1000 mg/d) was allowed. The intervention phase (median = 7.1 years), was followed by a postintervention phase (additional 13.8 years), which included 86.0% of the surviving women. A total of 595 incident DCIS cases were ascertained. Hazard ratios (HRs) plus 95% confidence intervals (CIs) were calculated. Results: The intervention group had a lower risk of DCIS throughout follow-up (HR = 0.82, 95% CI = 0.70 to 0.96) and during the postintervention phase (HR = 0.76, 95% CI = 0.61 to 0.94). The group that used CaD personal supplements in combination with the trial intervention had a lower risk of DCIS compared with the trial placebo group that did not use personal supplementation (HR = 0.72, 95% CI = 0.56 to 0.91). Conclusions: CaD supplementation in postmenopausal women was associated with reduced risk of DCIS, raising the possibility that consistent use of these supplements might provide long-term benefits for the prevention of DCIS.

Low-Fat Dietary Modification and Risk of Ductal Carcinoma In Situ of the Breast in the Women's Health Initiative Dietary Modification Trial.

BACKGROUND: Results of observational studies of the association between dietary fat and risk of invasive breast cancer have been inconsistent. In the Women's Health Initiative dietary modification (DM) randomized trial designed to lower fat intake, the intervention was not associated with a statistically significant reduction of overall breast cancer risk. However, the DM association with risk of ductal carcinoma in situ (DCIS) of the breast, a putative breast cancer precursor, has not been reported. METHODS: A total of 48,835 postmenopausal women, ages 50-79 years at enrollment, with no breast cancer history and ≥32% of total energy intake from fat, were randomly assigned either to a dietary intervention (n = 19,541) designed to reduce total fat intake to 20% of energy and to increase vegetable, fruit, and grain consumption, or to a comparison group (n = 29,294). Cox proportional hazards models were used to estimate HRs and 95% confidence intervals for the association between the intervention and DCIS risk. RESULTS: During 18.7 years (median) cumulative follow-up, including intervention (∼8.7 years) and post-intervention phases (∼13.0 years), 817 DCIS cases were ascertained. No evidence of an association between the DM intervention and DCIS risk was observed overall, or by trial phase (intervention and post-intervention). Similarly, no associations were found in subgroups defined by potential risk factors for DCIS. CONCLUSIONS: DM aiming to reduce fat intake was not associated with altered risk of DCIS. IMPACT: These results do not provide evidence of an association between dietary fat reduction and the risk of DCIS among postmenopausal women.

Upgrade rates and outcomes of screen-detected atypical intraductal epithelial proliferation (AIDEP) diagnosed on core needle biopsy.

INTRODUCTION: Atypical intraductal epithelial proliferation (AIDEP) is a breast lesion categorised as "indeterminate" if identified on core needle biopsy (CNB). The rate at which these lesions are upgraded following diagnostic excision varies in the literature. Women diagnosed with AIDEP are thought to be at increased risk of breast cancer. Our aim was to identify the rate of upgrade to invasive or in situ carcinoma in a group of patients diagnosed with AIDEP on screening mammography and to quantify their risk of subsequent breast cancer. METHODS: We conducted a retrospective review of a prospectively maintained database containing all patients diagnosed with AIDEP on CNB between 2005 and 2012 in an Irish breast screening centre. Basic demographic data was collected along with details of the original CNB result, rate of upgrade to carcinoma and details of any subsequent cancer diagnoses. RESULTS: In total 113 patients were diagnosed with AIDEP on CNB during the study period. The upgrade rate on diagnostic excision was 28.3% (n = 32). 6.2% (n = 7) were upgraded to invasive cancer and 22.1% (n = 25) to DCIS. 81 patients were not upgraded on diagnostic excision and were offered 5 years of annual mammographic surveillance. 9.88% (8/81) of these patients went on to receive a subsequent diagnosis of malignancy. The mean time to diagnosis of these subsequent cancers was 65.41 months (range 20.18-145.21). CONCLUSION: Our data showing an upgrade rate of 28% to carcinoma reflects recently published data and we believe it supports the continued practice of excising AIDEP to exclude co-existing carcinoma.

Epidemiologic risk factors for in situ and invasive ductal breast cancer among regularly screened postmenopausal women by grade in the Cancer Prevention Study-II Nutrition Cohort.

PURPOSE: Histopathologic grade provides an integrated measure of biologic features which affects cancer prognosis. In invasive ductal breast cancer (IDBC), the grade of the ductal carcinoma in situ (DCIS) and invasive components are usually concordant, suggesting grade is established early in tumorigenesis and may be linked to etiologic factors. In this study, we used prospectively collected data from postmenopausal women in the Cancer Prevention Study-II (CPS-II) Nutrition Cohort to compare risk factor associations among low-grade and high-grade DCIS, as well as low-grade and high-grade IDBC. METHODS: Among 73,825 cancer-free women at enrollment in the CPS-II Nutrition Cohort in 1992-1993 (mean age: 62.1 years), we verified 802 diagnosed with DCIS (C50 8500/2; n = 430 low-grade and 372 high-grade) and 3,125 with IDBC (C50 8500/3; n = 2,221 low-grade and 904 high-grade) through June 2013. Person-time contribution was conditional on screening mammograms self-reported on biennial surveys. Multivariable-adjusted joint Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: A personal history of benign breast disease was more strongly associated with higher risk of low-grade DCIS (HR = 2.20, 95% CI 1.81-2.67; p for heterogeneity = 0.0004) than high-grade DCIS. Consumption of two or more alcoholic drinks/day was only associated with a higher risk of low-grade IDBC (HR = 1.58, 95% CI 1.33-1.88; p for heterogeneity = 0.005). CONCLUSIONS: These results suggest heterogeneity by grade for breast cancer etiology. Identification of potential risk factor differences among low-grade and high-grade DCIS and IDBC may help to clarify associations, and ultimately, improve breast cancer risk prediction models.

Trends in Unilateral and Contralateral Prophylactic Mastectomy Use in Ductal Carcinoma In Situ of the Breast: Patterns and Predictors.

BACKGROUND: Increased use of contralateral prophylactic mastectomy (CPM) as treatment for ductal carcinoma in situ (DCIS) in the US was first noted in the early 2000s. Optimization of treatment guidelines for DCIS requires an understanding of current surgical treatment trends, particularly as they may differ by patient sociodemographic and community resource factors. OBJECTIVE: The aim of this study was to evaluate surgical treatment trends among US women with DCIS and to assess the impact of sociodemographic and community resource factors on surgical treatment choice. METHODS: The Surveillance, Epidemiology, and End Results dataset was queried for women aged 40 years and older who were diagnosed with unilateral DCIS between 2000 and 2014. Annual mastectomy rates were compared over time by age and race/ethnicity. Multivariable logistic regressions were performed to identify predictors of mastectomy use, with patient sociodemographics, tumor characteristics, and community resource factors (i.e. plastic surgeon density) as covariates. RESULTS: A total of 130,731 women with DCIS met the inclusion criteria. Overall mastectomy rates remained relatively unchanged over the study period (25-30%). CPM use increased for all age and race/ethnic groups, with the greatest increase exhibited by women aged 40-49 years [relative to 2000; 2014 odds ratio (OR) 10.6]. With respect to community resource factors, CPM use, as opposed to unilateral mastectomy, was associated with counties of higher education level (OR 1.52), higher income level (OR 1.22), and lower plastic surgeon density (OR 1.26). CONCLUSION AND RELEVANCE: While the popularity of mastectomy in the management of DCIS has remained relatively unchanged since the turn of the century, the use of CPM has risen substantially. Younger women with DCIS have seen the greatest increase in CPM use, a choice that remains influenced by race/ethnicity as well as income, education, and health resource availability. Until clinical risk stratifiers of DCIS are identified, the surgical decision-making paradigm must be improved so that treatment choice remains sensitive to cultural differences but becomes independent of income, education, and health resource availability.

Potential role of abbreviated MRI for breast cancer screening in an academic medical center.

The purpose is to determine whether an abbreviated MRI protocol (ABMR) is ready to be used for breast cancer screening in an academic practice setting. Two hundred and fifty nine breast MRIs from 1/1/2012 to 6/30/2012 were retrospectively reviewed using ABMR (MIP, Pre-contrastT1, single dynamic post-contrastT1, and subtraction). Five breast radiologists (4-28 year-expr) participated in this reader study performed in two phases: Phase1 - radiologist's privy to clinical history but not to comparison imaging. Phase2 - radiologists provided comparison imaging. For phase1, studies were reviewed using three steps: (a) MIP only (positive/negative/intermediate); (b) ABMR (recall/no recall) and (c) With T2 (for changes in recommendations). Radiologist also recorded total time for interpretation. In Phase2 the MRIs coded as "recall" were re-reviewed with available comparison studies, noting changes in final recommendation. The abnormal interpretation rates (AIRs) were calculated for phase1 and phase2 results with comparison to the original full protocol. Of the 259 patients (avg. age-52 years; range 26-78), there were seven cancers (three invasive, three DCIS and one breast lymphoma). Acquisition time for ABMR was 3 minutes, ABMR + T2-8 minutes, and original full protocol 16 minutes. Average MIP was positive or indeterminate in 86% (6/7) and negative in 14% (1/7) cancers. The average AIR for MIP only was 20.8% (sens-77.1%; spec-80.8%. The AIR w/o comparisons was 25.6% (sens-91.4%; spec- 76.2%); however the average AIR decreased in phase 2 with comparisons to 13.7% (sens-91.4%; spec-88.5%). The AIR of the original full protocol read was 16.2% (sens-100%; spec-85.7%). Addition of T2 changed assessment in only 3% (1.2%-6.5%). Avg. read time for ABMR including T2 was 2.5 minutes (1.6-4.0 minutes). ABMR is reliable for breast cancer screening, with acceptable interpretation time and acceptable AIR.

Performance measures among non-immigrants and immigrants attending BreastScreen Norway: a population-based screening programme.

OBJECTIVES: To explore performance measures among non-immigrants and immigrants attending BreastScreen Norway. METHODS: We analysed data from 2,951,375 screening examinations among non-immigrants and 153,026 among immigrants from 1996 to 2015. Immigrants were categorised into high- and low-incidence countries according to the incidence of breast cancer in their birth country. Performance measures, including attendance and recall rates, rates of screen-detected cancer (SDC) and interval breast cancer (IBC), positive predictive value (PPV) and histopathological tumour characteristics, were analysed. We used Fisher's exact model and t tests for descriptive statistics, and Poisson regression, adjusting for age and screening history, comparing results for non-immigrants versus immigrants. RESULTS: Attendance rates were 78% for non-immigrants and 56% for immigrants (p < 0.001). Rates of prevalent screens were 24% for non-immigrants and 32% for immigrants (p < 0.001). Immigrants from low-incidence countries were younger at diagnosis than non-immigrants (57 years versus 60 years, p < 0.001). Recall rates were 3.1% for non-immigrants and 3.8% for immigrants (p < 0.001), while PPVs were 17% and 14% (p < 0.001), respectively. IBCs in immigrants from low-incidence countries were more often triple negative (RRadj 1.81, 95% CI 1.11-2.94) than those in non-immigrants. Both SDC and IBC in immigrants from low-incidence countries tended more often to be histological grade 3 than those in non-immigrants. CONCLUSION: Immigrants had lower attendance rates, higher recall rates and lower PPV than non-immigrants. The optimal age range and screening interval for immigrant women from low-incidence countries need to be further investigated. KEY POINTS: • Immigrants from countries with a low incidence of breast cancer had their breast cancer diagnosed at a younger age than non-immigrants. • Interval breast cancers detected in immigrants from countries with a low incidence of breast cancers were more often triple negative than those in non-immigrants. • The optimal age range and screening interval for immigrant women from low-incidence countries and non-immigrants might differ.

Comparing Therapeutic versus Prophylactic Nipple-Sparing Mastectomy: Does Indication Inform Oncologic and Reconstructive Outcomes?

BACKGROUND: Initially performed only in prophylactic cases, indications for nipple-sparing mastectomy have expanded. Trends and surgical outcomes stratified by nipple-sparing mastectomy indication have not yet been fully examined. METHODS: Demographics and outcomes for all nipple-sparing mastectomies performed from 2006 to 2017 were compared by mastectomy indication. RESULTS: A total of 1212 nipple-sparing mastectomies were performed: 496 (40.9 percent) for therapeutic and 716 (59.1 percent) for prophylactic indications. Follow-up time was similar between both the therapeutic and prophylactic nipple-sparing mastectomy groups (47.35 versus 46.83 months, respectively; p = 0.7942). Therapeutic nipple-sparing mastectomies experienced significantly greater rates of major (p = 0.0165) and minor (p = 0.0421) infection, implant loss (p = 0.0098), reconstructive failure (p = 0.0058), and seroma (p = 0.0043). Rates of major (p = 0.4461) and minor (p = 0.2673) mastectomy flap necrosis and complete (p = 0.3445) and partial (p = 0.7120) nipple necrosis were equivalent. The overall rate of locoregional recurrence/occurrence per nipple-sparing mastectomy was 0.9 percent: 2.0 percent in therapeutic nipple-sparing mastectomies and 0.1 percent in prophylactic nipple-sparing mastectomies (p < 0.0001). CONCLUSIONS: Approximately 40 percent of nipple-sparing mastectomies are currently performed for therapeutic indications. Therapeutic nipple-sparing mastectomies had higher rates of infectious complications and reconstructive failure. Rates of locoregional cancer recurrence/occurrence are low, but occur significantly more often after therapeutic nipple-sparing mastectomy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Factors associated with the increasing trend of contralateral prophylactic mastectomy among patients with ductal carcinoma in situ: Analysis of Surveillance, Epidemiology, and End Results data.

PURPOSE: Our study aimed to investigate the factors influencing trends of contralateral prophylactic mastectomy (CPM) among patients with unilateral ductal carcinoma in situ (DCIS). PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) data to identify patients with unilateral DCIS diagnosed from 1998 to 2013. Patients were categorized as breast-conserving surgery (BCS), Unilateral Mastectomy and CPM group. Univariate and multivariate logistic regressions were applied to assess the factors associated with undergoing CPM among mastectomy patients. The trends of CPM among mastectomy patients through year were presented by different subgroups of sociodemographic and pathological characteristics. RESULTS: Of those, 105326 patients with DCIS were identified, and 6370 patients underwent CPM. The proportion of CPM was 6.05% for all surgically-treated patients and 21.09% for mastectomy patients, and it increased more than six-fold between 1998 and 2013 (from 1.74% to 10.89% for all surgically-treated patients and from 5.44% to 37.47% for mastectomy patients). Younger age, white race, married status, smaller tumor size, positive ER and PR status were significantly associated with higher CPM proportion among mastectomy patients. The proportion of CPM was increasing through year, and the increasing trends were obvious in the subgroups of younger, white, married, metropolitan, with higher bachelor degree and higher median family income patients, while there were no apparent differences in the trends between subgroups of pathological characteristics. CONCLUSION: The trends of CPM among mastectomy patients were increasing through years and influenced by patients' sociodemographic characteristics, but not pathological characteristics.

Ultraviolet Radiation Inhibits Mammary Carcinogenesis in an ER-Negative Murine Model by a Mechanism Independent of Vitamin D3.

Three decades ago, the Garlands postulated that vitamin D3 produced in the skin by ultraviolet radiation (UVR)-induced conversion of 7-dehydrocholesterol to pre-D3 has anticancer effects, thus triggering more than 9,500 publications on D3 and cancer. Here, we report that UVR treatment of transgenic mice of the well-established C3(1)/SV40 Tag mammary cancer model significantly inhibits both autochthonous carcinogenesis and allograft tumor growth, but in contrast neither dietary nor topical D3 influences mammary carcinogenesis in this specific mouse model. Furthermore, UVR's inhibitory effects occur irrespective of whether or not the treatment increases circulating D3 in the mice. The inhibitory effect of UVR on autochthonous tumors occurs at or before the stage of ductal carcinoma in situ. Our studies indicate clearly that UVR can exert D3-independent anticancer effects in C3(1)/SV40 Tag mice. Therefore, supplemental D3 may not mimic all possible beneficial effects of UVR, and uncovering non-D3-mediated mechanisms of UVR tumor inhibition may lead to novel strategies for cancer prevention. Cancer Prev Res; 11(7); 383-92. ©2018 AACR.

Optimal Duration of Extended Adjuvant Endocrine Therapy for Early Breast Cancer; Results of the IDEAL Trial (BOOG 2006-05).

Background: The optimal duration of extended endocrine therapy beyond five years after initial aromatase inhibitor-based adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer is still unknown. Therefore, we conducted a clinical trial to compare two different extended endocrine therapy durations. Methods: In the randomized phase III IDEAL trial, postmenopausal patients with hormone receptor-positive breast cancer were randomly allocated to either 2.5 or five years of letrozole after the initial five years of any endocrine therapy. The primary end point was disease free survival (DFS), and secondary end points were overall survival (OS), distant metastasis-free interval (DMFi), new primary breast cancer, and safety. Hazard ratios (HRs) were determined using Cox regression analysis. All analyses were by intention-to-treat principle. Results: A total of 1824 patients were assigned to either 2.5 years (n = 909) or five years (n = 915) of letrozole, with a median follow-up of 6.6 years. A DFS event occurred in 152 patients in the five-year group, compared with 163 patients in the 2.5-year group (HR = 0.92, 95% confidence interval [CI] = 0.74 to 1.16). OS (HR = 1.04, 95% CI = 0.78 to 1.38) and DMFi (HR = 1.06, 95% CI = 0.78 to 1.45) were not different between both groups. A reduction in occurrence of second primary breast cancer was observed with five years of treatment (HR = 0.39, 95% CI = 0.19 to 0.81). Subgroup analysis did not identify patients who benefit from five-year extended therapy. Conclusion: This study showed no superiority of five years over 2.5 years of extended adjuvant letrozole after an initial five years of adjuvant endocrine therapy.

Detection Rates of Ductal Carcinoma in Situ with Biennial Digital Mammography Screening: Radiologic Findings Support Pathologic Model of Tumor Progression.

Purpose To compare detection rates of ductal carcinoma in situ (DCIS), classified according to nuclear grade, between the prevalence round (baseline screening) and two subsequent screening rounds of a population-based digital mammography screening program, to assess differences over time. Materials and Methods The cancer registry provided data for 1970 graded pure DCIS cases from 16 screening regions of the prevalence round (baseline screening, from 2005 to 2008), first subsequent round, and second subsequent round; the interval between all screening rounds was 22-30 months. Age-adjusted logistic regression analysis was performed to compare the grade-specific detection rates between the prevalence round (reference) and subsequent screening rounds. Results Over all screening rounds, cancer detection rates were lowest for low-grade DCIS (range, 0.11 [58 of 508 817 patients] to 0.25 [178 of 713 867 patients] per 1000 women screened) and highest for high-grade DCIS (range, 0.53[271 of 508 817 patients] to 0.59 [237 of 398 944 patients] per 1000 women screened). Detection rates for low-grade DCIS were significantly lower in the first (odds ratio [OR] = 0.45, P < .001) and second (OR = 0.57, P < .001) subsequent screening rounds compared with that in the prevalence round; the relative reduction of detection rates of intermediate-grade DCIS was less pronounced (OR = 0.79, P = .006 and OR = 0.76, P = .003, respectively). Conversely, the detection rate of high-grade DCIS remained at the high level found in the prevalence screening (OR = 0.89, P = .143 and OR = 0.97, P = .700, respectively). Conclusion The findings demonstrate persistently high detection rates of high-grade DCIS in two consecutive subsequent screening rounds compared with the prevalence round; conversely, rates of low-grade DCIS and, less markedly, intermediate-grade DCIS decreased in subsequent rounds. Grade-related changes of DCIS detection are suggestive of distinct dynamics of lesion progression. © RSNA, 2017 An earlier incorrect version of this article appeared online. This article was corrected on November 10, 2017.

Ductal carcinomas in situ and invasive cancers detected on screening mammography: Cost-effectiveness of initial and subsequent rounds of population-based program 2007-2014.

BACKGROUND: Potential benefits of screening need to be carefully balanced against the financial burden for the national health care system. OBJECTIVES: To assess the cost-effectiveness of population-based mammographic screening in the 3-million region of Lower Silesia (Poland) after initial and 3 subsequent rounds. MATERIAL AND METHODS: Data was collected in a prospective manner using the databases of the official computer system for the monitoring of prophylaxis programs (SIMP), National Health Fund (Lower Silesia Regional Branch) and the Lower Silesia Cancer Registry. The expenses from each analyzed year were obtained from the Regional Coordinating Center for Screening Programs. The number of screen-detected and pathologically proven invasive and ductal in situ cancers was calculated. Costs of cancer detection were measured, converted into US dollars (USD), and expressed in 2015 USD using the comparison of purchasing power of money calculated with the Consumer Price Index. RESULTS: The total expense for the screening program in the initial round (2007-2008), first (2009-2010), second (2011-2012) and third (2013-2014) subsequent rounds was 4 732 383, 6 043 509, 6 484 834, and 5 900 793 USD whereas the number of cancer detected was 1049, 987, 1312, and 1070. The costeffectiveness ratio obtained in the program for each year was 4511, 6123, 4943, and 5515 USD per cancer found. The average cost of breast cancer detection in screening program in the region of Lower Silesia in years 2007-2014 was 5243 USD. CONCLUSIONS: The low cost of breast cancer detection in mammographic screening program makes it applicable for the health care systems in emerging economies.

Highlights of the San Antonio Breast Cancer Symposium 2016.

The 39th annual San Antonio Breast Cancer Symposium (SABCS) was convened in San Antonio, Texas, on 9-13 December 2016. More than 7000 clinicians and scientists from around the world participated in the symposium which featured a range of presentations and keynote talks pertaining to breast cancer screening, prevention, locoregional and systemic therapies. This two-part report highlights a selection of important studies presented at this premier breast cancer event with Part 1 focusing onmetastatic breast cancer, extended endocrine therapy and the prognostic significance of BRCA1/2 gene mutations. The second part of this report will discuss a range of topics including anti-HER2 directed treatments, the impact of radiotherapy on implant and autologous flap based reconstruction, biological risk predictors for ductal carcinoma-in situ (DCIS), longer term effects of dietary fat modification and the influence of aromatase inhibitors on endothelial cell function.

Body weight and sensitivity of screening mammography.

AIM: Obese women tend to participate less in breast cancer screening than normal weight women. However, obese women have fattier breast than normal weight women, and screening mammography works better in fatty than in dense breasts. One might, therefore, hypothesise that obese women would actually benefit more from screening than other women. METHODS: We combined data from the Danish Diet, Cancer and Health study and the organised population-based screening mammography programme in Copenhagen, Denmark. Women were categorised according to body mass index (BMI) (<20; 20 to <25; 25 to <30; 30 to <35, and 35+). We measured recall rate, sensitivity and specificity for subsequent screens with a 2-year follow-up period. RESULTS: The study included 6787 women. The recall rate varied from 1.4% for women with BMI <20 to 1.9% for women with BMI 35+, test for trend p = 0.86. Sensitivity varied from 42% (95% confidence interval [CI] 20-64%) for women with BMI <20 to 100% (95% CI 69-100%) for women with BMI 35+, test for trend p = 0.015. Specificity was fairly constant across BMI levels, being on average 98.8%, test for trend p = 0.79. CONCLUSION: This study showed that obese women were the ones with the highest sensitivity of screening mammography, while the specificity of screening remained stable across weight groups. Screening programmes should be organized to encourage these women to overcome obstacles for participation.

Analysis of Immune Cells from Human Mammary Ductal Epithelial Organoids Reveals Vδ2+ T Cells That Efficiently Target Breast Carcinoma Cells in the Presence of Bisphosphonate.

Developing strategies to enhance cancer prevention is a paramount goal, particularly given recent concerns about surgical treatment of preinvasive states such as ductal carcinoma in situ. Promoting effective immunosurveillance by leukocytes that scan for nascent neoplastic transformations represents a potential means to achieve this goal. Because most breast cancers arise within the ductal epithelium, enhancing protective immunosurveillance will likely necessitate targeting one or more of the distinctive lymphocyte types found in these sites under normal conditions. Here, we have characterized the intraepithelial lymphocyte compartment of non-cancerous human breast tissue and identified a subset of T lymphocytes that can be pharmacologically targeted to enhance their responses to breast cancer cells. Specifically, Vδ2(+) γδ T cells were consistently present in preparations of mammary ductal epithelial organoids and they proliferated in response to zoledronic acid, an aminobisphosphonate drug. Vδ2(+) T cells from breast ductal organoids produced the antitumor cytokine IFNγ and efficiently killed bisphosphonate-pulsed breast carcinoma cells. These findings demonstrate the potential for exploiting the ability of Vδ2(+) γδ T cells to respond to FDA-approved bisphosphonate drugs as a novel immunotherapeutic approach to inhibit the outgrowth of breast cancers.

Uptake of exemestane chemoprevention in postmenopausal women at increased risk for breast cancer.

Despite their efficacy, uptake of selective estrogen receptor modulators for breast cancer chemoprevention remains low. Exemestane, an aromatase inhibitor, has recently been identified as a potential chemopreventive option with fewer serious side effects compared with selective estrogen receptor modulators in postmenopausal women. The purpose of this study was to assess the uptake of exemestane in a breast cancer prevention clinic. A retrospective chart review was conducted to capture chemoprevention uptake by postmenopausal women presenting to the Yale Breast Cancer Prevention Clinic between November 2011 and November 2012. Descriptive statistics of the study population have been presented. Statistical analyses were carried out using SAS 9.3 (SAS Institute Inc., Cary, North Carolina, USA) between December 2012 and February 2013. Of 90 postmenopausal women, 56 were eligible for chemoprevention. Their mean age was 56.8 years. Among the women, 39% had osteopenia or osteoporosis. Thirteen women chose to start chemoprevention medication (23%). Although 31% of the chemopreventive medication administered included exemestane, only four of 56 postmenopausal women opted for exemestane (7%). Chemoprevention uptake rates of postmenopausal women in the setting of a breast cancer prevention clinic are higher than that reported in the general population; however, they remain low overall despite the inclusion of exemestane as an option. A significant proportion of postmenopausal women have decreased bone density, which is a potential barrier to exemestane uptake. The results provide practical implications suggesting that exemestane may have limited impact on breast cancer chemoprevention uptake. Further investigations should focus on understanding the factors that influence, predict, and increase chemoprevention uptake.

Use of immediate breast reconstruction and choice for contralateral prophylactic mastectomy.

BACKGROUND: Rates of contralateral prophylactic mastectomy (CPM) have been increasing nationally. The goal of this study was to evaluate recent trends in rates of CPM and immediate breast reconstruction (IBR). METHODS: After institutional review board approval, we evaluated all surgical procedures for women with newly diagnosed unilateral stages 0-III breast cancer from January 2009 to December 2014. Patients opting for therapeutic mastectomy were classified as either unilateral mastectomy or bilateral mastectomy, if CPM was performed, and according to whether or not they underwent IBR. Analysis was performed using trend tests for univariate associations and both binary and multinomial logistic regression for multivariate analysis. RESULTS: There were 3,195 women who underwent surgery for breast cancer--51% lumpectomy, 49% therapeutic mastectomy. Of the 1,571 patients undergoing therapeutic mastectomy, 829 (53%) underwent bilateral mastectomy. The rates of therapeutic mastectomy did not change over the study period (P = .92), but the use of IBR among patients undergoing therapeutic mastectomy increased from 37% in 2009 to 68% in 2014 (P < .0001). The use of bilateral mastectomy with IBR increased from 26% in 2009 to 46% in 2014 (P < .0001), whereas conversely the use of bilateral mastectomy without IBR decreased from 22% to 12% (P < .0001). IBR was associated with bilateral mastectomy; 69% of patients opting for IBR also underwent bilateral mastectomy compared with 38% choosing bilateral mastectomy in the group without IBR (adjusted odds ratio, 2.7; 95% CI, 2.1-3.5; P < .0001). CONCLUSION: Over recent years, rates of bilateral mastectomy have remained high. The use of IBR increased substantially for women undergoing therapeutic mastectomy and women undergoing IBR were significantly more likely to opt for bilateral mastectomy. The availability of IBR may influence patients' decisions to pursue bilateral mastectomy.