Do non-classic invasive lobular carcinomas derive a benefit from neoadjuvant chemotherapy?

PURPOSE: Invasive lobular breast cancers (ILCs) respond poorly to neoadjuvant chemotherapy (NAC). The degree of benefit of NAC among non-classic ILC (NC-ILC) variants compared with classic ILCs (C-ILCs) is unknown. METHODS: Consecutive patients with Stage I-III ILC treated from 2003 to 2019 with NAC and surgery were identified, and grouped as C-ILC or NC-ILC as per the original surgical pathology report, with pathologist (A.G.) review performed if original categorization was unclear. A subset of similarly treated invasive ductal cancers (IDCs) was identified for comparison. Clinicopathologic characteristics and pathologic complete response (pCR) rates were evaluated. RESULTS: Of 145 patients with ILC, 101 (70%) were C-ILC and 44 (30%) were NC-ILC (IDC cohort: 1157 patients). ILC patients were older, more often cT3/T4 and cN2/N3, and less often high-grade compared to IDC patients. Those with NC-ILC were less often ER+/HER2- (55% versus 93%), and more often HER2 + (25% versus 7%) and TN (21% versus 0%, all p < 0.001). Breast pCR was more common among NC-ILC, but most frequent in IDC. Nodal pCR rates were also lowest among C-ILC patients, but similar among NC-ILC and IDC patients. On multivariable analysis, C-ILC (OR 0.09) and LVI (OR 0.51) were predictive of lack of breast pCR; non-ER+/HER2- subtypes and breast pCR were predictive of nodal pCR. When our analysis was repeated with patients stratified by receptor subtype, histology was not independently predictive of either breast or nodal pCR. CONCLUSION: NC-ILC patients were significantly more likely to achieve breast and nodal pCR compared with C-ILC patients, but when stratified by subtype, histology was not independently predictive of breast or nodal pCR.

Pregnancy-associated breast cancer: does timing of presentation affect outcome?

PURPOSE: Pregnancy-associated breast cancer (PABC) comprises breast cancer diagnosed during the gestational period or within 12 months postpartum. While the incidence of PABC appears to be increasing, data regarding prognosis remain limited. METHODS: Here we evaluate clinicopathologic features, treatments, and clinical outcomes among women with stage 0-III PABC diagnosed between 1992 and 2020. Comparisons were made between women who were diagnosed with PABC during gestation and those who were diagnosed within 12 months postpartum. RESULTS: A total of 341 women were identified, with a median age of 36 years (range 25-46). The pregnancy group comprised 119 (35%) women, while 222 (65%) women made up the postpartum group. Clinicopathologic features were similar between groups, with most patients being parous and presenting with stage I and II disease. Treatment delays were uncommon, with a median time from histologic diagnosis to treatment of 4 weeks for both groups. Recurrence-free survival was similar between groups: 67% at 10 years for both. While 10-year overall survival appeared higher in the postpartum group (83% versus 78%, p = 0.02), only the presence of nodal metastases was associated with an increased risk of death (hazard ratio 5.61, 95% CI 2.20-14.3, p < 0.001), whereas timing of diagnosis and receptor profile did not reach statistical significance. CONCLUSION: Clinicopathologic features of women with PABC are similar regardless of timing of diagnosis. While 10-year recurrence-free survival is similar between groups, 10-year overall survival is higher among women diagnosed postpartum; however, timing of diagnosis may not be the driving factor in determining survival outcomes.

The Impact of Breast-Conserving Surgery Re-excision on Patient-Reported Outcomes Using the BREAST-Q.

BACKGROUND: Approximately 14% of women undergoing breast-conserving surgery (BCS) require re-excision to achieve negative margins following the Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) margin guidelines, which may influence patient-reported outcomes (PROs). Few studies have assessed the impact of re-excision on PROs following BCS. PATIENTS AND METHODS: Women with stage 0-III breast cancer undergoing BCS who completed a BREAST-Q PRO measure from 2010 to 2016 were identified from a prospective database. Baseline characteristics were compared between women who underwent one BCS and those who underwent ≥ 1 re-excision surgery for positive margins (R-BCS). Linear mixed models were used to analyze associations between number of excisions and BREAST-Q scores over time. RESULTS: Of 2543 eligible women, 1979 (78%) had one BCS and 564 (22%) had R-BCS. Younger age, lower BMI, surgery pre-SSO Invasive Guidelines issuance, ductal carcinoma in situ (DCIS), multifocal disease, radiation therapy receipt, and endocrine therapy omission were more common in the R-BCS group. Breast satisfaction and sexual well-being were lower in the R-BCS group 2 years postoperatively. There were no differences in psychosocial well-being between groups over 5 years. On multivariable analysis, re-excision was associated with lower breast satisfaction and sexual well-being (p= 0.007 and p= 0.049, respectively), but there was no difference in psychosocial well-being (p= 0.250). CONCLUSIONS: Women with R-BCS had lower breast satisfaction and sexual well-being 2 years postoperatively, but this difference did not remain long term. Psychosocial well-being in women who underwent one BCS were largely comparable over time to the R-BCS group. These findings may help in counseling women who are concerned about satisfaction and quality-of-life outcomes with BCS if re-excision is necessary.

Long-Term Patient-Reported Outcomes Comparing Oncoplastic Breast Surgery and Conventional Breast-Conserving Surgery: A Propensity Score-Matched Analysis.

INTRODUCTION: Oncoplastic breast surgery (OBS) combines plastic surgery techniques with conventional breast-conserving surgery (BCS) and expands BCS eligibility. Limited data are available on patient-reported outcomes (PROs) after OBS. Here we compare long-term PROs after OBS and BCS utilizing the BREAST-Q. PATIENTS AND METHODS: Women undergoing OBS or BCS between 2006 and 2019 who completed ≥ 1 long-term BREAST-Q survey 3-5 years postoperatively were identified. Baseline characteristics were compared between women who underwent OBS/BCS. Women who underwent OBS were paired with those who underwent BCS using 1:2 propensity matching [by age, body mass index (BMI), race, T stage, and multifocality]. BREAST-Q scores were compared preoperatively and 3-5 years postoperatively. RESULTS: A total of 297 patients were included for analysis (99 OBS/198 BCS). Women who underwent OBS were younger (p < 0.001) and had higher BMI (p = 0.005) and multifocal disease incidence (p = 0.004). There was no difference between groups in nodal stage, re-excision rates, axillary surgery, chemotherapy, endocrine therapy, or radiotherapy. After propensity matching preoperatively, women who underwent OBS reported lower psychosocial well-being (63 versus 100, p = 0.039) but similar breast satisfaction and sexual well-being compared with women who underwent BCS; however, only three patients who underwent BCS had preoperative BREAST-Q scores available for review. In long-term follow-up, women who underwent OBS reported lower psychosocial scores (74 versus 93, p = 0.011) 4 years postoperatively, but not at 5 years (76 versus 77, p = 0.83). There was no difference in long-term breast satisfaction or sexual well-being. CONCLUSIONS: Women who undergo OBS present with a larger disease burden and may represent a group of non-traditional BCS candidates; they reported similar long-term breast satisfaction and sexual well-being compared with women who undergo BCS. While women who underwent OBS reported lower psychosocial well-being scores preoperatively and during a portion of the follow-up period, this difference was no longer seen at 5 years postoperatively.

Association of Moderate-Risk Breast Cancer Genes with Contralateral Prophylactic Mastectomy and Bilateral Disease.

BACKGROUND: The impact of ATM, CHEK2, and PALB2, the three most prevalent moderate-risk breast cancer genes, on surgical decision making is not well known. METHODS: Our retrospective study included patients with resectable non-metastatic breast cancer who underwent multigene panel testing between July 2014 and January 2020 with at least one genetic alteration (pathogenic or variant of uncertain significance [VUS] in ATM [n = 49], CHEK [n = 57], or PALB2 [n = 27]). Our objectives were to determine the rate of contralateral prophylactic mastectomy (CPM) and the rate of bilateral breast cancer. Univariable analyses (UVA) and multivariable analyses (MVA) were performed to identify factors associated with CPM and bilateral breast cancer. RESULTS: The rate of CPM was 39% (n = 49/127), with 54% (n = 25/46) of patients with a pathogenic mutation and 30% (n = 24/81) of patients with a VUS choosing CPM. On MVA, premenopausal status (odds ratio [OR] 3.46) and a pathogenic alteration (OR 3.01) were associated with increased use of CPM. Bilateral disease was noted in 16% (n = 22/138). Patients with pathogenic mutations had a 22% (n = 11/51) incidence of bilateral breast cancer, while patients with VUS had a 13% (n = 11/87) incidence, although this was not statistically significant on UVA or MVA. On MVA, premenopausal status was associated with a decreased risk of bilateral disease (OR 0.33, p = 0.022). During follow-up, a breast cancer event occurred in 16% (n = 22/138). CONCLUSIONS: Our study identified a high rate of CPM among those with ATM, CHEK2, and PALB2 alterations, including VUS. Further studies are needed to clarify reasons for CPM among patients with moderate-risk alterations.

Strategies to avoid mastectomy skin-flap necrosis during nipple-sparing mastectomy.

BACKGROUND: Nipple-sparing mastectomy is associated with a higher risk of mastectomy skin-flap necrosis than conventional skin-sparing mastectomy. There are limited prospective data examining modifiable intraoperative factors that contribute to skin-flap necrosis after nipple-sparing mastectomy. METHODS: Data on consecutive patients undergoing nipple-sparing mastectomy between April 2018 and December 2020 were recorded prospectively. Relevant intraoperative variables were documented by both breast and plastic surgeons at the time of surgery. The presence and extent of nipple and/or skin-flap necrosis was documented at the first postoperative visit. Necrosis treatment and outcome was documented at 8-10 weeks after surgery. The association of clinical and intraoperative variables with nipple and skin-flap necrosis was analysed, and significant variables were included in a multivariable logistic regression analysis with backward selection. RESULTS: Some 299 patients underwent 515 nipple-sparing mastectomies (54.8 per cent (282 of 515) prophylactic, 45.2 per cent therapeutic). Overall, 23.3 per cent of breasts (120 of 515) developed nipple or skin-flap necrosis; 45.8 per cent of these (55 of 120) had nipple necrosis only. Among 120 breasts with necrosis, 22.5 per cent had superficial, 60.8 per cent had partial, and 16.7 per cent had full-thickness necrosis. On multivariable logistic regression analysis, significant modifiable intraoperative predictors of necrosis included sacrificing the second intercostal perforator (P = 0.006), greater tissue expander fill volume (P < 0.001), and non-lateral inframammary fold incision placement (P = 0.003). CONCLUSION: Modifiable intraoperative factors that may decrease the likelihood of necrosis after nipple-sparing mastectomy include incision placement in the lateral inframammary fold, preserving the second intercostal perforating vessel, and minimizing tissue expander fill volume.

Impact of Endocrine Therapy Adherence on Outcomes in Elderly Women with Early-Stage Breast Cancer Undergoing Lumpectomy Without Radiotherapy.

BACKGROUND: National Comprehensive Center Network guidelines recommend radiotherapy (RT) omission in women age ≥ 70 years with estrogen receptor-positive (ER+), cN0, T1 tumors post-lumpectomy if they receive endocrine therapy (ET). However, little is known about the impact of poor adherence on locoregional recurrence (LRR) in elderly women forgoing RT. METHODS: Women age ≥ 70 years with pT1-2 ER+ breast cancer undergoing lumpectomy without RT from 2004 to 2019 were identified from a prospectively maintained database. ET adherence, calculated as treatment duration over follow-up time up to 5 years, was determined by chart review. We compared clinicopathologic characteristics and rates of LRR between women with high adherence (≥ 80%), low adherence (< 80%), and no ET. RESULTS: Of 968 women (27 bilateral cancers), adherence was high in 676 (70%) and low in 162 (17%); 130 (13%) took no ET. Younger age and use of aromatase inhibitor were associated with high adherence. On multivariable analysis, tumor size (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.03-2.68, p = 0.04) and high adherence (HR 0.13, 95% CI 0.07-0.26, p < 0.001) were significantly associated with LRR. At 53 months median follow-up, the 5-year rate of LRR was 3.1% (95% CI 2.4-3.9%) with high adherence, 14.7% (95% CI 11.7-17.7%) with low adherence, and 17.9% (95% CI 13.9-21.8%) with no ET (p < 0.01). CONCLUSIONS: Although adherence to ET was high overall, in the 30% of women with low adherence or no ET, LRR rates were significantly increased. Counseling regarding the distinct toxicities of ET and RT can help patients choose the therapy to which they will likely adhere to.

Timing of Presentation and Outcomes of Women with Stage IV Pregnancy-Associated Breast Cancer (PABC).

BACKGROUND: Pregnancy-associated breast cancer (PABC) and concurrent, or early development of, stage IV disease is uncommon. Given this rarity, and complexities surrounding pregnancy, data are limited regarding PABC treatment and outcomes. We evaluated oncologic, obstetric, and fetal outcomes of women with stage IV PABC in relation to presentation timing and treatment. PATIENTS AND METHODS: Our retrospective review of an institutional database identified women with stage IV PABC from 1998 to 2018. PABC was defined as diagnosis during pregnancy or ≤ 1 year postpartum. Clinicopathologic, treatment, and outcome variables were compared between women diagnosed during pregnancy versus postpartum. RESULTS: We identified 77 women (median age 35 years; interquartile range [IQR] 32-37 years): 51 (66%) in the postpartum group and 26 (34%) in the pregnant group, including 9 with therapeutic or spontaneous abortion. Among 17 women who continued pregnancy, no obstetric or fetal complications were noted. Clinicopathologic and treatment variables did not differ between groups. Of 43 women dead from disease, 15 had triple negative (TN) tumors. Median overall survival (OS) of TN tumors was 14 months (range 5-39 months); OS was associated with hormone receptor-positive and human epidermal growth factor receptor 2 (HER2) positive tumors (p < 0.01). At 31 months (range 0-137 months) median follow-up, the 5-year OS was 34% (95% confidence interval 21-46%), and did not differ among pregnant and postpartum groups (p = 0.2). CONCLUSIONS: Women with stage IV TN PABC had high mortality rates despite multimodality therapy. Timing of presentation did not affect management decisions or OS, even for women who completed pregnancy. Further research to understand PABC biology, focusing on TN tumors, is warranted.

Fertility Preservation in Young Women with Breast Cancer: Impact on Treatment and Outcomes.

BACKGROUND: The impact of chemotherapy timing on the fertility preservation (FP) decision is poorly understood. Here we evaluate factors associated with FP completion among women age ≤ 45 years with breast cancer who received chemotherapy and consulted with a reproductive endocrinology and infertility (REI) specialist, and report pregnancy and oncologic outcomes. PATIENTS AND METHODS: This retrospective review included all women age ≤ 45 years diagnosed with stage I-III unilateral breast cancer at Memorial Sloan Kettering Cancer Center between 2009 and 2015 who received chemotherapy and consulted with an REI specialist. Clinicopathologic features and factors associated with the decision to undergo FP were analyzed, and comparisons were made with the Wilcoxon rank-sum test, Chi-square test, or Fisher's exact test. Survival curves were constructed using the Kaplan-Meier method. RESULTS: Among the 172 women identified, median age was 34 years (interquartile range 31-37 years). The majority of women were single (n = 99, 57.6%) and nulliparous (n = 134, 77.9%). Most women underwent FP (n = 121, 70.3%). Factors associated with the decision to undergo FP included younger median age (33 vs. 37 years, p < 0.001), having private insurance (p < 0.001), nulliparity (p < 0.001), and referral from Breast Surgery (p = 0.004). Tumor characteristics and treatments were similar between women who underwent FP and those who declined. Overall survival and recurrence-free survival were also similar between groups. Women who underwent FP were more likely to have a biological child after breast cancer treatment. CONCLUSIONS: Women underwent FP at high rates independent of timing of chemotherapy and oncologic factors. FP is associated with having a biological child and does not compromise oncologic outcomes.

The Effect of Age on Outcomes After Neoadjuvant Chemotherapy for Breast Cancer.

BACKGROUND: Younger women (age ≤ 40 years) with breast cancer undergoing neoadjuvant chemotherapy (NAC) have higher rates of pathologic complete response (pCR); however, it is unknown whether axillary or breast downstaging rates differ by age. In this study, we compared pCR incidence and surgical downstaging rates of the breast and axilla post NAC, between patients aged ≤ 40, 41-60, and ≥ 61 years. METHODS: We identified 1383 women with stage I-III breast cancer treated with NAC and subsequent surgery from November 2013 to December 2018. pCR and breast/axillary downstaging rates were assessed and compared across age groups. RESULTS: Younger women were significantly more likely to have ductal histology, poorly differentiated tumors, and BRCA mutations; 35% of tumors were hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-), 36% were HER2-positive (HER2+), and 29% were triple negative (TN), with similar subtype distribution across age groups (p = 0.6). Overall, pCR rates did not differ by age, however among patients with TN tumors (n = 394), younger women had higher pCR rates (52% vs. 35% among those aged 41-60 years and 29% among those aged ≥61 years; p = 0.007) and were more likely to have tumors with high tumor-infiltrating lymphocyte (TIL) concentrations (p < 0.001). Downstaging to breast-conserving surgery (BCS) eligibility post NAC among initially BCS-ineligible patients was similar across age groups; younger women chose BCS less often (p < 0.001). Among cN1 patients (n = 813), 52% of women ≤40 years of age avoided axillary lymph node dissection (ALND) with NAC, versus 39% and 37% in the older groups (p < 0.001). CONCLUSIONS: Younger women undergoing NAC for axillary downstaging were more likely to avoid ALND across all subtypes; however, overall pCR rates did not differ by age. Despite equivalent breast downstaging and BCS eligibility rates across age groups, younger women were less likely to undergo BCS.

Opportunities for Improvement in the Administration of Neoadjuvant Chemotherapy for T4 Breast Cancer: A Comparison of the U.S. and Nigeria.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is an integral component of T4 breast cancer (BCa) treatment. We compared response to NAC for T4 BCa in the U.S. and Nigeria to direct future interventions. MATERIALS AND METHODS: Cross-sectional retrospective analysis included all patients with non-metastatic T4 BCa treated from 2010 to 2016 at Memorial Sloan Kettering Cancer Center (New York, New York) and Obafemi Awolowo University Teaching Hospitals Complex (Ile Ife, Nigeria). Pathologic complete response (pCR) and survival were compared and factors contributing to disparities evaluated. RESULTS: Three hundred and eight patients met inclusion criteria: 157 (51%) in the U.S. and 151 (49%) in Nigeria. All U.S. patients received NAC and surgery compared with 93 (62%) Nigerian patients. Fifty-six out of ninety-three (60%) Nigerian patients completed their prescribed course of NAC. In Nigeria, older age and higher socioeconomic status were associated with treatment receipt. Fewer patients in Nigeria had immunohistochemistry performed (100% U.S. vs. 18% Nigeria). Of those with available receptor subtype, 18% (28/157) of U.S. patients were triple negative versus 39% (9/23) of Nigerian patients. Overall pCR was seen in 27% (42/155) of U.S. patients and 5% (4/76) of Nigerian patients. Five-year survival was significantly shorter in Nigeria versus the U.S. (61% vs. 72%). However, among the subset of patients who received multimodality therapy, including NAC and surgery with curative intent, 5-year survival (67% vs. 72%) and 5-year recurrence-free survival (48% vs. 61%) did not significantly differ between countries. CONCLUSION: Addressing health system, socioeconomic, and psychosocial barriers is necessary for administration of complete NAC to improve BCa outcomes in Nigeria. IMPLICATIONS FOR PRACTICE: This cross-sectional retrospective analysis of patients with T4 breast cancer in Nigeria and the U.S. found a significant difference in pathologic complete response to neoadjuvant chemotherapy (5% Nigeria vs. 27% U.S.). Five-year survival was shorter in Nigeria, but in patients receiving multimodality treatment, including neoadjuvant chemotherapy and surgery with curative intent, 5-year overall and recurrence-free survival did not differ between countries. Capacity-building efforts in Nigeria should focus on access to pathology services to direct systemic therapy and promoting receipt of complete chemotherapy to improve outcomes.

Adoption of SSO-ASTRO Margin Guidelines for Ductal Carcinoma in Situ: What Is the Impact on Use of Additional Surgery?

BACKGROUND: Historically, more than one-third of patients with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) underwent additional surgery. The SSO-ASTRO guidelines advise 2 mm margins for patients with DCIS having BCS and whole-breast radiation (WBRT). Here we examine guideline impact on additional surgery and factors associated with re-excision. PATIENTS AND METHODS: Patients treated with BCS for pure DCIS from August 2015 to January 2018 were identified. Guidelines were adopted on September 1, 2016, and all patients had separately submitted cavity-shave margins. Clinicopathologic characteristics, margin status, and rates of additional surgery were examined. RESULTS: Among 650 patients with DCIS who attempted BCS, 50 (8%) converted to mastectomy. Of 600 who had BCS as final surgery, 336 (56%) received WBRT and comprised our study group. One hundred twenty-eight (38%) were treated pre-guideline and 208 (62%) were treated post-guideline. Characteristics and margin status were similar between groups. The re-excision rate was 38% pre-guideline adoption and 29% post-guideline adoption (p = 0.09), with 91% having only one re-excision. Re-excision for ≥ 2 mm margins was uncommon (6% pre-guideline vs. 5% post-guideline). On multivariate analysis, younger age (OR 0.97, 95% CI 0.94-0.99, p = 0.02) and larger DCIS size (OR 1.43, 95% CI 1.2-1.8, p < 0.001) were predictive of re-excision; guideline era was not. Younger age (OR 0.93, 95% CI 0.9-0.97, p < 0.001) and larger size (OR 1.64, 95% CI 1.3-2.1, p < 0.001) were predictive of conversion to mastectomy, but residual tumor burden was low. CONCLUSIONS: The SSO-ASTRO guidelines did not significantly change re-excision rates for DCIS in our practice, likely since re-excision for margins ≥ 2 mm was uncommon even prior to guideline adoption, dissimilar to historically observed variations in surgeon practices. Younger age and larger DCIS size were associated with additional surgery.

Tumor-Nipple Distance of ≥ 1 cm Predicts Negative Nipple Pathology After Neoadjuvant Chemotherapy.

BACKGROUND: As neoadjuvant chemotherapy (NAC) for breast cancer has become more widely used, so has nipple-sparing mastectomy. A common criterion for eligibility is a 1 cm tumor-to-nipple distance (TND), but its suitability after NAC is unclear. In this study, we examined factors predictive of negative nipple pathologic status (NS-) in women undergoing total mastectomy after NAC. METHODS: Women with invasive breast cancer treated with NAC and total mastectomy from August 2014 to April 2018 at our institution were retrospectively identified. Following review of pre- and post-NAC magnetic resonance imaging (MRI) and mammograms, the association of clinicopathologic and imaging variables with NS- was examined and the accuracy of 1 cm TND on imaging for predicting NS- was determined. RESULTS: Among 175 women undergoing 179 mastectomies, 74% of tumors were cT1-T2 and 67% were cN+ on pre-NAC staging; 10% (18/179) had invasive or in situ carcinoma in the nipple on final pathology. On multivariable analysis, after adjusting for age, grade, and tumor stage, three factors, namely number of positive nodes, pre-NAC nipple-areolar complex retraction, and decreasing TND, were significant predictors of nipple involvement (p < 0.05). The likelihood of NS- was higher with increasing TND on pre- and post-NAC imaging (p < 0.05). TND ≥ 1 cm predicted NS- in 97% and 95% of breasts on pre- and post-NAC imaging, respectively. CONCLUSIONS: Increasing TND was associated with a higher likelihood of NS-. A TND ≥ 1 cm on pre- or post-NAC imaging is highly predictive of NS- and could be used to determine eligibility for nipple-sparing mastectomy after NAC.

Surgical ovarian suppression for adjuvant treatment in hormone receptor positive breast cancer in premenopausal patients.

OBJECTIVE: Ovarian suppression is recommended to complement endocrine therapy in premenopausal women with breast cancer and high-risk features. It can be achieved by either medical ovarian suppression or therapeutic bilateral salpingo-oophorectomy. Our objective was to evaluate characteristics of patients with stage I-III hormone receptor positive primary breast cancer who underwent bilateral salpingo-oophorectomy at our institution. MATERIALS AND METHODS: Premenopausal women with stage I-III hormone receptor positive primary breast cancer diagnosed between January 2010 and December 2014 were identified from a database. Patients with confirmed BRCA1/2 mutations were excluded. Distribution of characteristics between treatment groups was assessed using χ2 test and univariate logistic regression. A multivariate model was based on factors significant on univariate analysis. RESULTS: Of 2740 women identified, 2018 (74%) received endocrine treatment without ovarian ablation, 516 (19%) received endocrine treatment plus ovarian ablation, and 206 (7.5%) did not receive endocrine treatment. Among patients undergoing ovarian ablation 282/516 (55%) received medical ovarian suppression, while 234 (45%) underwent bilateral salpingo-oophorectomy. By univariate logistic analyses, predictors for ovarian ablation were younger age (OR 0.97), histology (other vs ductal: OR 0.23), lymph node involvement (OR 1.89), higher International Federation of Gynecology and Obstetrics (FIGO) stage (stage II vs I: OR 1.48; stage III vs I: OR 2.86), higher grade (grade 3 vs 1: OR 3.41; grade 2 vs 1: OR 2.99), chemotherapy (OR 1.52), and more recent year of diagnosis (2014 vs 2010; OR 1.713). Only year of diagnosis, stage, and human epidermal growth factor receptor 2 (HER-2) treatment remained significant in the multivariate model. Within the cohort undergoing ovarian ablation, older age (OR 1.05) was associated with therapeutic bilateral salpingo-oophorectomy. Of 234 undergoing bilateral salpingo-oophorectomy, 12 (5%) mild to moderate adverse surgical events were recorded. CONCLUSIONS: Bilateral salpingo-oophorectomy is used frequently as an endocrine ablation strategy. Older age was associated with bilateral salpingo-oophorectomy. Perioperative morbidity was acceptable. Evaluation of long-term effects and quality of life associated with endocrine ablation will help guide patient/provider decision-making.

Contralateral Prophylactic Mastectomy Use After Neoadjuvant Chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) for breast cancer increases breast-conserving surgery (BCS) rates, but many women opt for mastectomy with contralateral prophylactic mastectomy (CPM). Here we evaluate factors associated with CPM use in women undergoing mastectomy post-NAC. METHODS: A retrospective institutional NAC database review identified women with clinical stage I-III, unilateral invasive breast cancer undergoing unilateral mastectomy (UM) or CPM mastectomy from 9/2013 to 12/2017. Clinical/pathologic characteristics, imaging, and presence of contraindications to BCS post-NAC were compared, with subset analysis of BCS candidates. The multivariable analysis was adjusted for potential confounders. RESULTS: Five hundred sixty-nine women underwent mastectomy after NAC, 297 (52%) UM and 272 (48%) CPM. On univariable analysis, younger age, BRCA+, lower pre-NAC clinical stage, pathologic complete response, and axillary surgery extent were associated with CPM (all p < 0.01). Favorable post-NAC clinical factors of no residual palpable disease, clinically negative nodes, complete response on breast imaging, and no post-NAC contraindication to BCS were also associated with CPM (all p < 0.01). On multivariable analysis, young age (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.91-0.95), lower pre-NAC stage (OR 0.51, 95% CI 0.34-0.77), and no contraindication to BCS (OR 3.12, 95% CI 2.02-4.82) were significantly associated with CPM. Among the 203 (35%) women who had no contraindications to BCS post-NAC, 145 (71%) underwent CPM. BRCA+ and family history were reasons more frequently cited for mastectomy among CPM than UM (p < 0.001). CONCLUSIONS: CPM was performed in 48% of women undergoing mastectomy after NAC; younger women with earlier-stage cancers were more likely to undergo CPM. While increased use of CPM in women with more favorable disease is medically appropriate, our findings indicate a lost opportunity for use of BCS.

Does Use of Neoadjuvant Chemotherapy Affect the Decision to Pursue Fertility Preservation Options in Young Women with Breast Cancer?

BACKGROUND: The American Society of Clinical Oncology guidelines recommend early referral to reproductive endocrinology and infertility (REI) specialists for young women diagnosed with breast cancer. Current practice patterns demonstrate an increased utilization of neoadjuvant chemotherapy (NAC). We evaluated premenopausal women with breast cancer after consultation with a Fertility Nurse Specialist (FNS) and determine factors associated with referral to REI specialists. METHODS: This retrospective review included all premenopausal women diagnosed at our institution with stage 0-III unilateral breast cancers between 2009 and 2015 who completed an FNS consultation. Clinicopathologic features and factors associated with referral to REI after FNS consultation were analyzed. RESULTS: A total of 334 women were identified. Median age was 35 years (interquartile range 32-38). The majority of women were single (n = 198, 59.3%) and nulliparous (n = 239, 71.6%). REI referrals were common (n = 237, 71.0%). The Breast Surgery service was the most frequent referring service (n = 194, 58.1%), with significantly more REI referrals compared to Breast Medicine and Genetics services (p = 0.002). Nulliparity was associated with REI referral (p < 0.0001). Adjuvant chemotherapy (p = 0.003) was associated with pursuing REI referral, whereas NAC (p < 0.001) was associated with declining REI referral. CONCLUSIONS: Most women elected to consult with an REI specialist, confirming strong interest in fertility preservation among premenopausal women with breast cancer. However, women receiving NAC more frequently declined referral to REI, suggesting that the need to start NAC may influence decisions regarding fertility preservation. With increasing utilization of NAC, our study supports the need for further counseling and education regarding fertility preservation for women undergoing NAC.

Increase in Utilization of Nipple-Sparing Mastectomy for Breast Cancer: Indications, Complications, and Oncologic Outcomes.

BACKGROUND: Nipple-sparing mastectomy (NSM) is increasingly performed for invasive breast cancer. Growing evidence supporting the oncologic safety of NSM has led to its widespread use and broadened indications. In this study, we examine the indications, complications, and long-term outcomes of therapeutic NSM. METHODS: From 2003 to 2016, women undergoing NSM for invasive cancer or ductal carcinoma in situ (DCIS) were identified from a prospectively maintained database. Patient and disease characteristics were compared by procedure year, while complications were compared by procedure year using generalized mixed-effects models accounting for a random surgeon effect. Overall survival and time to recurrence were examined. RESULTS: Of the 467 therapeutic NSMs, 337 (72%) were invasive cancer, 126 (27%) were DCIS, and 4 (1%) were phyllodes tumors. Median age was 45 years (range 24-75) and median follow-up among survivors was 39.4 months. Three hundred and fifty-seven (76.4%) cases were performed in 2011 or after. When comparing NSMs performed before and after 2011, there was a significant increase in NSMs performed for invasive tumors (58% vs. 77%; p < 0.001). There was no difference in family history, genetic mutations, smoking status, neoadjuvant chemotherapy, prior radiation, nodal involvement, or tumor subtype. Twenty-one (4.5%) nipple excisions were performed, of which 14 were performed for cancer at the nipple margin. Forty-four breasts (9.4%) had complications that required re-operation. Fifteen patients had locoregional recurrence or distant metastasis. CONCLUSIONS: NSM use for invasive carcinoma has doubled at our institution since 2011, while postoperative complications and recurrence rates remain low. Our experience supports the selective use of NSM in the malignant setting with careful patient selection.

Microscopic Extracapsular Extension in Sentinel Lymph Nodes Does Not Mandate Axillary Dissection in Z0011-Eligible Patients.

BACKGROUND: In the ACOSOG (American College of Surgeons Oncology Group) Z0011 trial and the AMAROS (After Mapping of the Axilla: Radiotherapy or Surgery?) trial, matted nodes with gross extracapsular extension (ECE), a risk factor for locoregional recurrence, were an indication for axillary lymph node dissection (ALND), but the effect of microscopic ECE (mECE) in the sentinel lymph nodes (SLNs) on recurrence was not examined. METHODS: Between 2010 and 2017, 811 patients with cT1-2N0 breast cancer and SLN metastasis were prospectively managed according to Z0011 criteria, with ALND for those with more than two positive SLNs or gross ECE. Management of mECE was not specified. In this study, we compare outcomes of patients with one to two positive SLNs with and without mECE, treated with SLN biopsy alone (n = 685). RESULTS: Median patient age was 58 years, and median tumor size was 1.7 cm. mECE was identified in 210 (31%) patients. Patients with mECE were older, had larger tumors, and were more likely to be hormone receptor positive and HER2 negative, have two positive SLNs, and receive nodal radiation. At a median follow-up of 41 months, no isolated axillary failures were observed. There were 11 nodal recurrences; two supraclavicular ± axillary, four synchronous with breast, and five with distant failure. The five-year rate of any nodal recurrence was 1.6% and did not differ by mECE (2.3% vs. 1.3%; p = 0.84). No differences were observed in local (p = 0.08) or distant (p = 0.31) recurrence rates by mECE status. CONCLUSIONS: In Z0011-eligible patients, nodal recurrence rates in patients with mECE are low after treatment with SLN biopsy alone, even in the absence of routine nodal radiation. The presence of mECE should not be considered a routine indication for ALND.

Management of ipsilateral supernumerary nipple at time of breast cancer diagnosis.

Supernumerary breast components occur predominantly between the breast and umbilicus. Carcinoma of this ectopic, or accessory breast tissue (ABT), is exceedingly rare, accounting for <1% of breast cancer cases. Historically, ectopic breast carcinoma was considered aggressive with poor outcome. In 1995, Evans et al reported 90 cases spanning from 1929 to 1993 with a 9.4% survival beyond 4 years. More contemporary studies reveal improvement in both treatment and survival. There is currently no consensus on whether prophylactic excision of an ipsilateral supernumerary nipple at the time of initial breast cancer diagnosis is necessary. The following describes a patient with an ipsilateral tumor uniquely located within her supernumerary nipple 5 years after mastectomy.

Does race predict survival for women with invasive breast cancer?

BACKGROUND: Black women with breast cancer have lower survival rates and higher recurrence rates in comparison with white women. This study compared treatment and survival outcomes for black and white women at a highly specialized tertiary care cancer center. METHODS: An institutional review board-approved, retrospective institutional database review was performed to identify all black women treated for invasive breast cancer between 2005 and 2010. Women with a prior history of breast cancer, stage IV cancer, or bilateral breast cancer were excluded. White women had similar exclusion criteria applied and were then matched to black women 1:1 by age and diagnosis year. Clinicopathologic and treatment variables were compared by race. Kaplan-Meier methodology was used to estimate overall survival (OS) and disease-free survival (DFS); a multivariable analysis was conducted with Cox regression models. RESULTS: The study group consisted of 1332 women (666 black). The median tumor size was larger in black women (1.6 vs 1.3 cm; P < .001). Black women had more nodal disease (41.1% vs 32%; P < .001) and had tumors that were more frequently an estrogen receptor-negative (32.9% vs 15%; P < .001), progesterone receptor-negative (47.1% vs 30.2%; P < .001), or triple-negative (TN) subtype (24% vs 8.9%; P < .001) in comparison with white women. Black women also had inferior DFS and OS; race was not an independent prognostic indicator in the multivariable analysis. CONCLUSIONS: Black women had more advanced disease and adverse prognostic indicators at diagnosis, but race was not an independent predictor of outcome. Black women were significantly more likely to have TN breast cancer. Further research is necessary to understand the differences in tumor biology associated with race.