Faculty Bibliography

IMPORTANCE/OBJECTIVE:Prospective trials have demonstrated sentinel lymph node (SLN) false-negative rates of less than 10% when 3 or more SLNs are retrieved in patients with clinically node-positive breast cancer rendered clinically node-negative with neoadjuvant chemotherapy (NAC). However, rates of nodal recurrence in such patients treated with SLN biopsy (SLNB) alone are unknown because axillary lymph node dissection (ALND) was performed in all patients, limiting adoption of this approach. OBJECTIVE:To evaluate nodal recurrence rates in a consecutive cohort of patients with clinically node-positive (cN1) breast cancer receiving NAC, followed by a negative SLNB using a standardized technique, and no further axillary surgery. DESIGN, SETTING, AND PARTICIPANTS/METHODS:From November 2013 to February 2019, a cohort of consecutively identified patients with cT1 to cT3 biopsy-proven N1 breast cancer rendered cN0 by NAC underwent SLNB with dual tracer mapping and omission of ALND if 3 or more SLNs were identified and all were pathologically negative. Metastatic nodes were not routinely clipped, and localization of clipped nodes was not performed. The study was performed in a single tertiary cancer center. INTERVENTION/METHODS:Omission of ALND in patients with cN1 breast cancer after NAC if 3 or more SLNs were pathologically negative. MAIN OUTCOME AND MEASURES/METHODS:The primary outcome was the rate of nodal recurrence among patients with cN1 breast cancer treated with SLNB alone after NAC. RESULTS:Of 610 patients with cN1 breast cancer treated with NAC, 555 (91%) converted to cN0 and underwent SLNB; 234 (42%) had 3 or more negative SLNs and had SLNB alone. The median (IQR) age of these 234 patients was 49 (40-58) years; median tumor size was 3 cm; 144 (62%) were ERBB2 (formerly HER2)-positive, and 43 (18%) were triple negative. Most (212 [91%]) received doxorubicin-based NAC; 205 (88%) received adjuvant radiotherapy (RT), and 164 (70%) also received nodal RT. At a median follow-up of 40 months, there was 1 axillary nodal recurrence synchronous with local recurrence in a patient who refused RT. Among patients who received RT (n = 205), there were no nodal recurrences. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:This cohort study found that in patients with cN1 disease rendered cN0 with NAC, with 3 or more negative SLNs with SLNB alone, nodal recurrence rates were low, without routine nodal clipping. These findings potentially support omitting ALND in such patients.

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.

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.

BACKGROUND:Despite limited evidence regarding its safety, immediate reconstruction (IR) is increasingly offered to women with T4 breast cancer. We compared outcomes after IR, delayed reconstruction (DR), and no reconstruction (NR) in patients treated with neoadjuvant chemotherapy (NAC) and postmastectomy radiation therapy (PMRT) for T4 disease. STUDY DESIGN:We retrospectively identified consecutive women with T4 tumors treated with trimodality therapy from January 2007 through December 2019. Clinicopathologic characteristics, complications requiring reoperation, time to PMRT, and recurrence patterns were compared. The cumulative incidence of local recurrence (LR) was estimated using Kaplan-Meier methods. RESULTS:Of the 269 women identified, the median (IQR) age was 52 (45-62) years; 164 women (61%) had T4d disease. Forty-five women (17%) had IR, 41 (15%) had DR, and 183 (68%) had NR. IR was independently associated with T4a-c disease (odds ratio [OR], 5.75; 95% CI, 2.57-12.87; p < 0.001) and younger age (OR 0.91; 95% CI, 0.86-0.94; p < 0.001). The risk of complications after IR was 22% overall and 46% in T4d patients (6/13), compared with 4.4% overall for NR and 7.3% for DR (p < 0.001). IR was associated with >8-week interval to PMRT (p < 0.001). At a median (range) follow-up of 4.2 (0.2-13) years, the median time to first recurrence was 18 months and was similar between groups (p = 0.13). The cumulative incidence of LR was 16% for T4d disease and 2.2% for T4a-c disease (p < 0.001). CONCLUSIONS:After IR, women with T4 tumors, particularly T4d disease, experienced delayed initiation of adjuvant treatment and substantial morbidity, suggesting that an interval of >18 months between mastectomy and reconstruction is advisable.

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: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.

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/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.

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.

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.