Background In breast cancer patients with nodal metastases at presentation, false-negative rates <10% have been demonstrated for sentinel node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) when ≥3 negative sentinel nodes (SLNs) are retrieved, but the frequency with which axillary dissection (ALND) can be avoided is uncertain. Methods Among 534 prospectively identified consecutive patients with clinical stage II–III cancer receiving NAC from 11/2013–11/2015, all biopsy-proven node-positive (N+) cases were identified. Patients who were clinically node-negative post-NAC were SLNB-eligible. ALND was indicated for failed mapping, <3 SLNs retrieved, or positive SLNs. Results Of 288 N+ patients, 195 completed surgery. 132/195 (68%) were SLNB-eligible. Of these, median age was 50yrs, 73(55%) were ER+, 21(16%) ER−/HER2+, 38(29%) triple negative. SLNB was deferred intraoperatively in 4 cases. Among 128 SLNB attempts, ≥3 SLNs were retrieved in 110 (86%), 1–2 SLNs in 15(12%), 3 (2%) failed mapping. ALND was indicated in 66 cases: 54(82%) for positive SLNs, 9(14%) for <3 negative SLNs, 3(4%) for failed mapping. 17% with <3 negative SLNs retrieved had persistent disease. 62/128 (48%) had SLNB alone with ≥3 SLNs retrieved. Among 195 N+ patients completing surgery, nodal pathologic complete response (pCR) was achieved in 49%, ranging from 21% in ER+/HER2− to 97% in ER−/HER2+ cases, and was significantly more common than breast pCR in ER+/HER2− and triple-negative cases. Conclusions Nearly 70% of N+ patients were SLNB-eligible post-NAC. ALND was avoided in 48%, supporting the role of NAC in reducing the need for ALND among patients presenting with nodal metastases.

Importance The increasing use of neoadjuvant chemotherapy (NAC) for operable breast cancer has raised questions about optimal local therapy for the axilla. Observations Sentinel lymph node biopsy (SLNB) after NAC in patients presenting with clinically negative nodes has an accuracy similar to upfront SLNB and reduces the need for axillary lymph node dissection (ALND) compared to SLNB prior to NAC. In patients presenting with node-positive disease, clinical trials demonstrate that SLNB after NAC is accurate when ≥3 sentinel nodes are obtained, but long-term outcomes are lacking. The relative importance of pre- and post-NAC stage in predicting risk of locoregional recurrence remains an area of controversy. Conclusion and Relevance NAC reduces the need for ALND, and SLNB is an accurate method of determining nodal status post NAC.

Background Rates of mastectomy with immediate reconstruction are rising. Skin flap necrosis after this procedure is a recognized complication that can impact cosmetic outcomes and patient satisfaction, and, in worst cases, potentially delay adjuvant therapies. Many retrospective studies of this complication have identified variable event rates and inconsistent associated factors. Methods We designed a prospective study to capture the rate of skin flap necrosis and pre-, intra-, and post-operative variables with follow-up to 8 weeks post-operatively. Univariate and multivariate analyses were performed for factors associated with skin flap necrosis. Results Out of 606 consecutive procedures, 85 (14%) had some level of skin flap necrosis: 46 (8%) mild, 6 (1%) moderate, 31 (5%) severe, and 2 (0.3%) uncategorized. On univariate analysis for any necrosis, smoking, history of breast augmentation, nipple-sparing mastectomy, and time from incision to specimen removal were significant. In multivariate models, nipple-sparing, time from incision to specimen removal, sharp dissection, and previous breast reduction were significant for any necrosis. When looking only at moderate or severe necrosis, BMI, diabetes, nipple-sparing mastectomy, specimen size, and expander size were significant on univariate analysis. Nipple-sparing mastectomy and specimen size were significant on multivariate analysis. Nipple-sparing mastectomy was associated with higher rates of necrosis at every level of severity. Conclusions Rates of skin flap necrosis are likely higher than reported in retrospective series. Modifiable technical variables have limited impact on rates of necrosis. Patients with multiple risk factors should be counseled about the risks, especially if they are contemplating nipple-sparing mastectomy.

Purpose The increased breast cancer risk conferred by a diagnosis of lobular carcinoma in situ (LCIS) is poorly understood. Here we review our 29-year longitudinal experience with LCIS to evaluate factors associated with breast cancer risk. Methods Patients participating in surveillance following an LCIS diagnosis are followed in a prospectively maintained database. Comparisons were made among women choosing surveillance, with or without chemoprevention, and those undergoing bilateral prophylactic mastectomies between 1980 and 2009. Results 1060 patients with LCIS without concurrent breast cancer were identified. Median age at LCIS diagnosis was 50 years (range, 27–83). 56 (5%) underwent bilateral prophylactic mastectomy; 1004 chose surveillance with (n=173) or without (n=831) chemoprevention. At a median follow-up of 81 months (6–368 months), 150 patients developed 168 breast cancers (63% ipsilateral, 25% contralateral, 12% bilateral), with no dominant histology (ductal carcinoma in situ 35%, infiltrating ductal carcinoma 29%, infiltrating lobular carcinoma 27%, other 9%). Breast cancer incidence was significantly reduced in women taking chemoprevention (10-year cumulative risk: 7% chemoprevention; 21% no chemoprevention, p<.0001). In multivariate analysis, chemoprevention was the only clinical factor associated with breast cancer risk (hazard ratio 0.27, 95% confidence interval 0.15–0.50). In a subgroup nested case-control analysis, volume of disease defined as the ratio of slides with LCIS to total number of slides reviewed was also associated with breast cancer development (p=0.008). Conclusion We observed a 2% annual incidence of breast cancer among women with LCIS. Common clinical factors used for risk prediction including age and family history were not associated with breast cancer risk. The lower breast cancer incidence in women opting for chemoprevention highlights the potential for risk reduction in this population.

Objective To determine rates of axillary dissection (ALND) and nodal recurrence in patients eligible for ACOSOG Z0011. Summary Background Data Z0011 demonstrated that patients with cT1-2N0 breast cancers and 1–2 involved sentinel lymph nodes (SLNs) having breast-conserving therapy (BCT) had no difference in locoregional recurrence or survival after SLN biopsy alone or ALND. The generalizability of the results and importance of nodal radiotherapy (RT) is unclear. Methods Patients eligible for Z0011had SLN biopsy alone. Prospectively defined indications for ALND were metastases in ≥3 SLNs or gross extracapsular extension. Axillary imaging was not routine. SLN and ALND groups and radiation fields were compared with chi-square and t-tests. Cumulative incidence of recurrences was estimated with competing risk analysis. Results From 8/2010–12/2016, 793 patients met Z0011 eligibility criteria and had SLN metastases. 130 (16%) had ALND; ALND did not vary based on age, estrogen receptor, progesterone receptor, or HER2 status. 5-year event-free survival after SLN alone is 93% with no isolated axillary recurrences. Cumulative 5-year rates of breast+nodal and nodal+distant recurrence were each 0.7%. In 484 SLN-only patients with known RT fields (103 prone, 280 supine tangent, 101 breast+nodes) and follow-up≥12 months, the 5-year cumulative nodal recurrence rate was 1% and did not differ significantly by RT fields. Conclusions We confirm that even without preoperative axillary imaging or routine use of nodal RT, ALND can be avoided in a large majority of Z0011-eligible patients with excellent regional control. This approach has the potential to spare substantial numbers of women the morbidity of ALND.

Background In the setting where determining extent of residual disease is key for surgical planning after neoadjuvant chemotherapy (NAC), herein we evaluate reliability of MRI in predicting pathologic complete response (pCR) of the breast primary and axillary nodes following NAC. Study Design Patients who had MRI before and after NAC between 06/2014–08/2015 were identified in a prospective database following IRB approval. Post NAC-MRI of the breast and axillary nodes was correlated with residual disease on final pathology. PCR was defined as absence of invasive and in situ disease. Results We analyzed 129 breast cancers. Median patient age was 50.8 years (range 27.2–80.6). Tumors were HER2 amplified in 52/129 (40%), estrogen receptor-positive/HER2-negative in 46/129 (36%) and triple negative in 31/129 (24%), with respective pCR rates of 50%, 11% and 29%. Median tumor size pre- and post-NAC MRI were 4.1cm and 1.45cm, respectively. MRI had a positive predictive value of 63.4% (26/41) and negative predictive value of 84.1% (74/88) for in-breast pCR. Axillary nodes were abnormal on pre-NAC MRI in 97 cases; 65 had biopsy-confirmed metastases. The nodes normalized on post-NAC MRI in 33/65 (51%); axillary pCR was present in 22/33 (67%). In 32 patients with proven nodal metastases and abnormal nodes on post-NAC MRI, 11 achieved axillary pCR. In 32 patients with normal nodes on pre- and post-NAC MRI, 6 (19%) had metastasis on final pathology. Conclusions Radiologic complete response by MRI does not predict pCR with adequate accuracy to replace pathologic evaluation of the breast tumor and axillary nodes.

The appropriate negative margin width for women undergoing breast-conserving surgery for both ductal carcinoma in situ (DCIS) and invasive carcinoma is controversial. This review examines the available data on the margin status for invasive breast cancer and DCIS, and highlights the similarities and differences in tumor biology and standard treatments that affect the local recurrence (LR) risk and, therefore, the optimal surgical margin. Consensus guidelines support a negative margin, defined as no ink on tumor, for invasive carcinoma treated with breast-conserving therapy. Because of differences in the growth pattern and utilization of systemic therapy, a margin of 2 mm has been found to minimize the LR risk for women with DCIS undergoing lumpectomy and radiation therapy (RT). Wider negative margins do not improve local control for DCIS or invasive carcinoma when they are treated with lumpectomy and RT. Re-excision for negative margins should be individualized, and the routine practice of performing additional surgery to obtain a wider negative margin is not supported by the literature. Cancer 2018;124:1335-41. © 2018 American Cancer Society.

IMPORTANCEProspective 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 PARTICIPANTSFrom 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 Omission of ALND in patients with cN1 breast cancer after NAC if 3 or more SLNs were pathologically negative. MAIN OUTCOME AND MEASURESThe primary outcome was the rate of nodal recurrence among patients with cN1 breast cancer treated with SLNB alone after NAC. RESULTSOf 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 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.