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.

Does a brief surgeon training in negotiation theory principles decrease rates of contralateral prophylactic mastectomy?

PURPOSE: Despite the lack of any oncologic benefit, contralateral prophylactic mastectomy (CPM) use among women with unilateral breast cancer is increasing. This patient-driven trend is influenced by fear of recurrence and desire for peace of mind. Traditional educational strategies have been ineffective in reducing CPM rates. Here we employ training in negotiation theory strategies for counseling and determine the effect on CPM rates. METHODS: In consecutive patients with unilateral breast cancer treated with mastectomy from 05/2017 to 12/2019, we examined CPM rates before and after a brief surgeon training in negotiation skills. This comprised a systematic framework for patient counseling utilizing early setting of the default option, leveraging social proof, and framing. RESULTS: Among 2144 patients, 925 (43%) were treated pre-training and 744 (35%) post-training. Those treated in the 6-month transition period were excluded (n = 475, 22%). Median patient age was 50 years; most patients had T1-T2 (72%), N0 (73%), and estrogen receptor-positive (80%) tumors of ductal histology (72%). The CPM rate was 47% pre-training versus 48% post-training, with an adjusted difference of -3.7% (95% CI -9.4 to 2.1, p = 0.2). In a standardized self-assessment survey, all 15 surgeons reported a high baseline use of negotiation skills and no significant change in conversational difficulty with the structured approach. CONCLUSION: Brief surgeon training did not affect self-reported use of negotiation skills or reduce CPM rates. The choice of CPM is a highly individual decision influenced by patient values and decision styles. Further research to identify effective strategies to minimize surgical overtreatment with CPM is needed.

Mutational Status is Associated with a Higher Rate of Pathologic Complete Response After Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer.

BACKGROUND: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) occurs in up to 20% of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancers. Whether this differs among BRCA mutation carriers is uncertain. This study compared pCR between BRCA1/2 mutation carriers and matched sporadic control subjects. METHODS: From November 2013 to January 2022, this study identified 522 consecutive women with clinical stage I to III HR+/HER2- breast cancer treated with NAC and surgery. The study matched BRCA1/2 mutation carriers 1:2 to non-carriers in terms of age, clinical tumor (cT) and nodal (cN) stage, and differentiation. Two-sample non-parametric tests compared baseline characteristics. Multivariable logistic regression assessed pCR (i.e., ypT0/ispN0) by BRCA1/2 mutational status. RESULTS: Of the 522 women (median age, 50 years), 59 had BRCA1/2 mutations, 78% of which were clinically node positive. Anthracycline-based NAC was administered to 97%. More BRCA1/2 mutation carriers were younger, had cT1 tumors, and had poorly differentiated disease. After matching, 58 BRCA1/2 mutation carriers were similar to 116 non-carriers in terms of age (p = 0.6), cT (p = 0.9), cN stage (p = 0.7), and tumor differentiation (p > 0.9). Among the mutation carriers, the pCR rate was 15.5% for BRCA1/2, 38% (8/21) for BRCA1, and 2.7% (1/37) for BRCA2 versus 7.8% (9/116) for the non-carriers (p < 0.001). After NAC, 5 (41.7%) of the 12 BRCA1 mutation carriers converted to pN0 versus 10 (37%) of the 27 BRCA2 mutation carriers and 19 (20.9%) of the 91 non-carriers (p = 0.3). In the multivariable analysis, BRCA1 mutation status was associated with higher odds of pCR than non-carrier status (odds ratio [OR] 6.31; 95% confidence interval [CI] 1.95-20.5; p = 0.002), whereas BRCA2 mutation status was not (OR 0.45; 95% CI 0.02-2.67; p = 0.5). CONCLUSIONS: This study showed that BRCA1 mutation carriers with HR+/HER2- breast cancers have a higher rate of pCR than sporadic cancers and may derive greater benefit from chemotherapy. The use of NAC to downstage these patients should be considered.

Is local recurrence higher among patients who downstage to breast conservation after neoadjuvant chemotherapy?

BACKGROUND: In early studies, local recurrence (LR) rates were higher after neoadjuvant chemotherapy (NAC) in comparison with upfront surgery. Modern outcomes are uncertain, particularly among those who are initially breast-conserving surgery-ineligible (BCSi) and downstage to being breast-conserving surgery-eligible (BCSe). METHODS: Among patients with cT1-3 breast cancer treated from 2014 to 2018 who were BCSe after NAC, clinicopathologic characteristics and LR were compared between initially BCSe patients and BCSi patients who downstaged. Breast-conserving surgery (BCS) eligibility was determined prospectively. RESULTS: Among 685 patients, 243 (35%) were BCSe before and after NAC and had BCS; 282 (41%) were BCSi before NAC, downstaged to BCSe, and had BCS; and 160 (23%) were BCSi before NAC, downstaged to BCSe, and chose mastectomy. The median age was 52 years, and most cancers were cT1-2 (84%), cN+ (61%), and human epidermal growth factor receptor 2-positive (HER2+; 38%) or triple-negative (34%). Those who were BCSe before NAC had a lower cT stage, whereas those who chose mastectomy were younger (P < .05). NAC was usually ACT (doxorubicin, cyclophosphamide, and a taxane)-based (92%), 99% of HER2+ patients received dual blockade, and 99% of BCS patients received adjuvant radiation. At a median follow-up of 35 months, 22 patients (3.2%) had developed LR. The Kaplan-Meier 4-year LR rates were not different among the groups (1.9% for those who were BCSe before and after NAC, 6.3% for those who downstaged to being BCSe and underwent BCS, and 2.7% for those who downstaged and underwent mastectomy; P = .17). CONCLUSIONS: LR rates are low after NAC and BCS, even among BCSi patients who downstage, and they are not improved in patients who downstage and choose mastectomy. Mastectomy can be safely avoided in BCSi patients who downstage with NAC.

Local Recurrence is Frequent After Heroic Mastectomy for Classically Inoperable Breast Cancers.

BACKGROUND: Despite advances in neoadjuvant systemic therapy (NST), some patients with aggressive T4 breast cancers do not respond. The efficacy of 'heroic' mastectomy in maintaining local control is unclear. METHODS: In consecutive patients with primary or recurrent T4 cancers with < 50% shrinkage on NST who underwent mastectomy from 2007 to 2017, clinicopathologic characteristics and locoregional recurrence (LRR) were examined. RESULTS: Among 104 patients, 59 (57%) had primary T4M0, 12 (12%) had locally recurrent T4M0, and 33 (32%) had T4M1 disease. Median age was 58.5 years and the majority had high-grade (74%) ductal cancers (85%); 45 (44%) were estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-), 26 (25%) were HER2 positive (HER2+), and 31 (30%) were triple negative (TN). Postoperative complications developed in 41 (39%) patients. At a median follow-up of 37 months, 42 (40%) patients developed LRR. TN (hazard ratio [HR] 7.5) and HER2+ (HR 2.67) subtypes, lymphovascular invasion (LVI; HR 3.80), and positive margins (HR 4.09) were predictive of LRR. The 3-year LRR rate was highest and overall survival (OS) was lowest among patients with TN cancers, at 66% (95% confidence interval [CI] 48-83%) and 30% (95% CI 14-47%), respectively. CONCLUSIONS: After heroic mastectomy, postoperative complications were frequent and LRR occurred in 40% of patients despite a median OS of 3.8 years. Among TN patients, the 3-year LRR rate of 66% and 3-year OS of 30% suggest limited surgery benefit. Careful patient selection is prudent when considering heroic mastectomy.

Margin Width and Local Recurrence in Patients Undergoing Breast Conservation After Neoadjuvant Chemotherapy.

BACKGROUND: A margin of "no ink on tumor" has been established for primary breast conservation therapy (BCT), but the appropriate margin following neoadjuvant chemotherapy (NAC) remains controversial. We examined the impact of margin width on ipsilateral breast tumor recurrence (IBTR) in the NAC-BCT population. METHODS: Consecutive patients receiving NAC-BCT were identified from a prospective database. The associations between clinicopathologic characteristics, margin width, and isolated IBTR were evaluated. RESULTS: From 2013 to 2019 we identified 582 patients with 586 tumors who received NAC-BCT. The median age of the cohort was 54 years (IQR 45, 62); 84% of patients had cT1/T2 tumors and 61% were clinically node positive. The majority of tumors were HER2+ (38%) or triple negative (TN) (31%). Pathologic complete response was observed in 29%. Margin width was > 2 mm in 517 tumors (88%) and ≤ 2 mm in 69 (12%). At a median follow-up of 39 months, 14 patients had IBTR as a first event, with 64% occurring within 24 months of surgery. The 4-year IBTR rate was 2% (95% CI 1-4%), and there was no difference based on margin width (3% ≤ 2 mm vs 2% > 2 mm; p = not significant). On univariate analysis, clinical and pathologic T stage and receptor subtype, but not margin width, were associated with IBTR (p < 0.05). On multivariable analysis, TN subtype and higher pathologic T stage were associated with isolated IBTR (both p < 0.05). CONCLUSION: Pathologic features and tumor biology, not margin width, were associated with IBTR in NAC-BCT patients.

Omission of Intraoperative Frozen Section May Reduce Axillary Overtreatment Among Clinically Node-Negative Patients Having Upfront Mastectomy.

BACKGROUND: The growing use of postmastectomy radiation/regional nodal irradiation (PMRT) has resulted in many women receiving both axillary dissection (ALND) and PMRT, increasing lymphedema rates. After developing standardized PMRT criteria, we adopted a policy of ALND omission among cN0 patients with 1-2 positive sentinel nodes (+SLNs) requiring PMRT. We evaluated how often overtreatment with ALND+PMRT was avoided with this approach. METHODS: A retrospective review of a prospectively maintained database was performed beginning 1 year before policy adoption. Intraoperative SLN evaluation was routine pre- and post-policy. ALND was performed for SLN macrometastasis pre-policy, and selectively performed post-policy for 1-2 +SLNs based on PMRT criteria. ALND+PMRT was required for ≥ 3 +SLNs. RESULTS: From March 1, 2018 to November 30, 2020, a total of 2207 cT1-3N0 patients had mastectomy and 231 had +SLNs; 109 (47%) were treated pre-policy and 122 (53%) post-policy. Most (81%) had 1-2 +SLNs. There was no change in rates of ALND+PMRT (64% pre-policy vs. 58% post-policy, p = 0.09), including in patients with 1-2 +SLNs (61% vs. 51%, p = 0.20). Post-policy, ALND was omitted in 9 (7%) patients recognized intraoperatively as PMRT candidates; avoidable ALND was performed in 40 (33%) patients not identified as PMRT candidates until receipt of final pathology. Overall, had intraoperative SLN evaluation been deferred, only 5.7% of patients would have required completion ALND: 2.2% (n = 49/2207) for ≥ 3 +SLNs and 3.5% (n = 77/2207) for 1-2 +SLNs without PMRT indication. CONCLUSIONS: Most patients could have avoided ALND+PMRT if decision making was deferred until final pathology was available. Selective intraoperative SLN evaluation in cN0 patients having upfront mastectomy may reduce avoidable overtreatment.

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.

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.

Extranodal Tumor Deposits in the Axillary Fat Indicate the Need for Axillary Dissection Among T1-T2cN0 Patients with Positive Sentinel Nodes.

BACKGROUND: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated the safety of omitting axillary lymph node dissection (ALND) in T1-T2cN0 patients with fewer than three positive sentinel nodes (SLNs) undergoing breast-conservation therapy. While microscopic extracapsular extension (mECE) > 2 mm is associated with increased nodal burden, the significance of extranodal tumor deposits (ETDs) in the axillary fat is uncertain. METHODS: Consecutive patients with T1-T2cN0 breast cancer undergoing sentinel node biopsy and ALND for SLN metastases from January 2010 to December 2018 were identified. ETDs were defined as intravascular tumor emboli or metastatic deposits in the axillary fat. Clinicopathologic characteristics and nodal burden were compared by ETD status. RESULTS: Among 1114 patients, 113 (10%) had ETDs: 81 (72%) were intravascular tumor emboli and 32 (28%) were soft tissue deposits. Patients with ETDs had larger tumors (median 2.2 vs. 2.1 cm; p = 0.033) and more often had mECE (83% vs. 44%; p < 0.001). On univariable analysis, presence of ETDs (odds ratio [OR] 9.66, 95% confidence interval [CI] 6.36-14.68), larger tumors (OR 1.47, 95% CI 1.25-1.72), and mECE (OR 10.73, 95% CI 6.86-16.78) were associated with four or more additional positive non-SLNs (NSLNs; all p < 0.001). On multivariable analysis, ETDs remained associated with four or more positive NSLNs (OR 5.67, 95% CI 3.53-9.08; p < 0.001). ETDs were strongly associated with four or more positive NSLNs (OR 7.15, 95% CI 4.04-12.67) among patients with one to two positive SLNs (n = 925). CONCLUSIONS: Among T1-T2cN0 patients with SLN metastases, ETDs are strongly associated with four or more positive NSLNs at ALND. Even among those who may otherwise meet the criteria for omission of ALND, the presence of ETDs in axillary fat warrants consideration of ALND.

Selecting Node-Positive Patients for Axillary Downstaging with Neoadjuvant Chemotherapy.

BACKGROUND: Axillary lymph node dissection (ALND) can be avoided in node-positive patients who receive neoadjuvant chemotherapy (NAC) if three or more negative sentinel lymph nodes (SLNs) are retrieved. We evaluate how often node-positive patients avoid ALND with NAC, and identify predictors of identification of three or more SLNs and of nodal pathological complete response (pCR). METHODS: From November 2013 to July 2019, all patients with cT1-3, biopsy-proven N1 tumors who converted to cN0 after NAC received SLN biopsy (SLNB) with dual mapping and were identified from a prospectively maintained database. RESULTS: 630 consecutive N1 patients were eligible for axillary downstaging with NAC; 573 (91%) converted to cN0 and had SLNB, and 531 patients (93%) had three or more SLNs identified. Lymphovascular invasion (LVI; odds ratio [OR] 0.46, 95% confidence interval [CI] 0.24-0.87; p = 0.02) and increasing body mass index (BMI; OR 0.77, 95% CI 0.62-0.96 per 5-unit increase; p = 0.02) were significantly associated with failure to identify three or more SLNs. 255/573 (46%) patients achieved nodal pCR; 237 (41%) had adequate mapping. Factors associated with ALND avoidance included high grade (OR 2.51, 95% CI 1.6-3.94, p = 0.001) and receptor status (HR+/HER2- [referent]: OR 1.99, 95% CI 1.15-3.46 [p = 0.01] for HR-/HER2-, OR 3.93, 95% CI 2.40-6.44 [p < 0.001] for HR+/HER2+, and OR 8.24, 95% CI 4.16-16.3 [p < 0.001] for HR-/HER2+). LVI was associated with a lower likelihood of avoiding ALND (OR 0.28, 95% CI 0.18-0.43; p < 0.001). CONCLUSIONS: ALND was avoided in 41% of cN1 patients after NAC. Increased BMI and LVI were associated with lower retrieval rates of three or more SLNs. ALND avoidance rates varied with receptor status, grade, and LVI. These factors help select patients most likely to avoid ALND.

Why Are There So Many Mastectomies in the United States?

Breast-conserving therapy (BCT) and mastectomy result in equivalent long-term survival. Locoregional recurrence rates after BCT have decreased over time and are now similar to those after mastectomy. Contralateral breast cancer rates are declining as well owing to the widespread use of adjuvant systemic therapy. Despite these improved outcomes, increasing rates of bilateral mastectomy for unilateral cancer have been observed in the United States. Medical indications for mastectomy are well defined and present in a minority of patients, and women at increased risk for contralateral cancer are a small proportion of the breast cancer population. Evidence indicates that increasing use of mastectomy is a patient-driven trend that is most pronounced among younger, educated, and well-insured women, and reflects fear of recurrence and in some cases misunderstanding of future cancer risks. Although satisfaction levels are generally high among patients choosing contralateral prophylactic mastectomy, complications and procedure extent may be underestimated. Improved communication strategies are essential to facilitate this complex decision-making process.

Lobular Histology Does Not Predict the Need for Axillary Dissection Among ACOSOG Z0011-Eligible Breast Cancers.

BACKGROUND: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that axillary lymph node dissection (ALND) may be omitted for women with two or fewer positive sentinel nodes (SLNs) undergoing breast-conservation therapy (BCT). Lobular histology comprises a minority of patients, and applicability to these discohesive cancers has been questioned. METHODS: From August 2010 to March 2017, patients undergoing BCT for cT1-2N0 cancer with positive SLNs were prospectively managed with ALND for three or more positive SLNs or gross extracapsular extension (ECE). In this study, clinicopathologic characteristics and nodal burden were compared between pure/mixed invasive lobular cancer (ILC) and invasive ductal cancer (IDC) patients. RESULTS: Among 813 consecutive patients, 104 (12.8%) had ILC and 709 (87.2%) had IDC. ILC was more often multifocal and low grade, and less frequently had lymphovascular invasion (all p < 0.001). ILC more often had SLN macrometastases (81.7% ILC vs. 69.4% IDC; p = 0.01) and more than 2 mm of ECE (30.8% ILC vs. 19.5% IDC; p = 0.03), but the proportions of cases with three or more positive SLNs were similar in the two groups (14.4% ILC vs. 9.9% IDC; p = 0.2). The ALND procedure was performed for 20 ILC patients (19.2%) compared with 97 IDC patients (13.7%) (p = 0.2). Additional positive nodes were found in 80% of the ILC patients versus 56.7% of the IDC patients (p = 0.09). The ALND and nodal burden rates were similar in the estrogen receptor-positive (ER+) subset analysis. In the multivariable analysis, lobular histology (p = 0.03) and larger tumors (p = 0.03) were associated with additional positive nodes. During a median follow-up period of 42 months, there were no isolated axillary recurrences. CONCLUSIONS: Despite a higher proportion of SLN macrometastases and association with more positive nodes at ALND, lobular histology does not predict the need for ALND. ALND is not indicated on the basis of histology among patients otherwise meeting Z0011 criteria.

Was Reexcision Less Frequent for Patients with Lobular Breast Cancer After Publication of the SSO-ASTRO Margin Guidelines?

BACKGROUND: The Society of Surgical Oncology and American Society for Radiation Oncology consensus guidelines defined a negative margin for breast-conserving surgery (BCS) as no ink on tumor, and implementation has reduced rates of additional surgery for patients with invasive ductal cancer (IDC). The outcomes for invasive lobular cancer (ILC) patients are uncertain. METHODS: This study identified patients who had stage 1 or 2 ILC treated with BCS from January 2010 to February 2018. The guidelines were adopted 1 January 2014. Clinicopathologic characteristics, margin status, and reexcisions were compared before and after adoption of the guidelines and with those of IDC patients treated from May 2013 to February 2015. RESULTS: Among 745 early-stage ILC patients undergoing BCT, 312 (42%) were treated before the guidelines and 433 (58%) after the guidelines. Most clinicopathologic characteristics were similar between the two groups, with differences in lobular carcinoma in situ, lymphovascular invasion, and node-positivity rates. The overall rates of additional surgery declined significantly after the guidelines (31.4 to 23.1%; p = 0.01), but the difference did not reach significance for reexcisions (19.9 to 15.2%; p = 0.12) or conversions to mastectomy (11.5 to 7.9%; p = 0.099) individually. Between eras, no difference in incidence or number of tumor on ink or ≤ 2 mm margins was observed (all p = 0.2). Larger tumors, younger age, and pre-guideline era were independently associated with additional surgery. Only younger age was predictive of mastectomy. Among 431 pre-guideline and 601 post-guideline IDC patients, reexcisions declined from 21.3 to 14.8% (p = 0.008), and conversion to mastectomy was rare (0.6%). The magnitude of reduction in any additional surgery (interaction, p = 0.92) and reexcisions (interaction, p = 0.56) was similar between ILC and IDC. CONCLUSIONS: Despite differences in growth pattern and conspicuity, guideline adoption significantly reduced additional surgery among ILC patients, with a magnitude of benefit similar to that among IDC patients.

Impact of Age on Locoregional and Distant Recurrence After Mastectomy for Ductal Carcinoma In Situ With or Without Microinvasion.

BACKGROUND: Locoregional recurrence (LRR) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) is increased in young women. We examined the impact of age on LRR and distant disease after mastectomy for DCIS ± microinvasion. METHODS: We identified consecutive patients with DCIS ± microinvasion treated with mastectomy from 1995 to 2017. LRR was defined as recurrence at the ipsilateral chest wall or regional nodes. RESULTS: Overall, 3121 cases were identified, of which 421 (13.5%) had DCIS + microinvasion. Median age was 49 years and median follow-up was 6.4 years; 821 were followed for 10 or more years. Thirty-four LRRs were observed: 33 (97%) were invasive, and 23 (68%) were in the chest wall alone. Cumulative 10-year LRR incidence was 1.4%. Age < 50 years, high grade, and DCIS + microinvasion were associated with LRR (p ≤ 0.001); however, margin status was not (p = 0.14). Adjusting for grade and DCIS + microinvasion, age < 50 years (hazard ratio [HR] 14.7, 95% confidence interval [CI] 3.5-61.5; p < 0.001) was associated with LRR. Compared with women ≥ 50 years of age, women age < 40 years had the highest risk (HR 27.0, 95% CI 6.0-121), and women age 40-49 years had intermediate risk (HR 11.8, 95% CI 2.8-50.5). The cumulative 10-year LRR incidence was 4.2% for women < 40 years of age, 2.0% for women 40-49 years of age, and 0.2% for women ≥ 50 years of age. Women age < 40 years had a 10-year distant disease rate of 1.6% versus women age 40-49 years (0.7%) and women age ≥ 50 years (0.7%) (log-rank p = 0.051). Grade, DCIS + microinvasion, and margins were unassociated with distant disease. CONCLUSIONS: LRR after mastectomy for DCIS ± microinvasion is uncommon, but is more frequent among women < 50 years of age, particularly in those < 40 years of age. The 10-year LRR rate in this youngest group remains low at 4.2%. Young age is an independent risk factor for LRR after BCS or mastectomy.

Is Clinical Exam of the Axilla Sufficient to Select Node-Positive Patients Who Downstage After NAC for SLNB? A Comparison of the Accuracy of Clinical Exam Versus MRI.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) endorses sentinel lymph node biopsy (SLNB) in patients with clinically positive axillary nodes who downstage after neoadjuvant chemotherapy (NAC). In this study, we compared the accuracy of post-NAC MRI to clinical exam alone in predicting pathologic status of sentinel lymph nodes in cN1 patients. METHODS: We identified patients with T0-3, N1 breast cancer who underwent NAC and subsequent SLNB from March 2014 to July 2017. Patients were grouped based on whether a post-NAC MRI was done. MRI accuracy in predicting SLN status was assessed versus clinical exam alone. RESULTS: A total of 450 patients met initial study criteria; 269 were analyzed after excluding patients without biopsy-confirmed nodal disease, palpable disease after NAC, and failed SLN mapping. Median age was 49 years. Post-NAC MRI was done in 68% (182/269). Patients undergoing lumpectomy vs mastectomy more frequently received a post-NAC MRI (88 vs 54%, p < 0.001). All other clinicopathologic parameters were comparable between those who did and did not have a post-NAC MRI. Thirty percent (55/182) had abnormal lymph nodes on MRI. Among these, 58% (32/55) had a positive SLN on final pathology versus 42% (53/127) of patients with no abnormal lymph nodes on MRI and 52% (45/87) of patients who had clinical exam alone (p = 0.09). MRI sensitivity was 38%, specificity was 76%, and overall SLN status prediction accuracy was 58%. CONCLUSIONS: Post-NAC MRI is no more accurate than clinical exam alone in predicting SLN pathology in patients presenting with cN1 disease. Abnormal lymph nodes on MRI should not preclude SLNB.

Treatment Strategies in Octogenarians with Early-Stage, High-Risk Breast Cancer.

BACKGROUND: Octogenarians with early-stage breast cancer often have low-risk tumor biology. However, optimal treatment strategies for those with high-risk biology remain unclear. METHODS: We reviewed the records of women ages 80-89 years with biopsy-proven, Stage I-II invasive breast cancer who were referred for surgical evaluation from January 2001 through December 2010. High-risk was defined as human epidermal growth factor receptor-positive (HER2+), triple-negative (TN), or histologic grade 3 disease. RESULTS: Among 178 patients, 40 (22%) were high-risk: 12 were grade 1-2 (10 HER2 + , 2 TN); 28 were grade 3 (7 HER2+, 6 TN, 15 estrogen receptor-positive (ER+)/HER2-). The high-risk group had larger tumors and more often had ductal histology and lymphovascular invasion than the low-risk group and was more likely to undergo mastectomy (18 vs. 5%, p = 0.02), radiotherapy (55 vs. 36%, p = 0.03), and chemotherapy (10 vs. 0%, p = 0.002). Endocrine therapy use was similar among ER+ patients in both groups. The four patients in the high-risk group given chemotherapy were HER2+ and received trastuzumab-based regimens, without any reported toxicities. At median follow-up of 67 months, 10% of the high-risk group had a recurrence (3 distant-only, 1 simultaneous locoregional and distant in a patient treated with mastectomy without radiotherapy). CONCLUSIONS: Tailored locoregional and systemic therapy resulted in low incidence of failure in these octogenarians with high-risk cancers with low morbidity. Modern adjuvant therapies should be considered for elderly women with high-risk cancers in the absence of significant comorbidities.

Are there patients with T1 to T2, lymph node-negative breast cancer who are "high-risk" for locoregional disease recurrence?

BACKGROUND: Indications for postmastectomy radiotherapy (PMRT) in patients with T1 to T2, lymph node-negative (N0) breast cancer with "high-risk" features are controversial. The European Organization for Research and Treatment of Cancer (EORTC) 22922 and National Cancer Institute of Canada Clinical Trials Group MA20 trials reporting improved 10-year disease-free survival with lymph node irradiation included patients with high-risk N0 disease, but, to the authors' knowledge, benefits in patients receiving modern systemic therapy are uncertain. METHODS: The authors retrospectively identified patients with T1 to T2N0 disease who were treated with mastectomy from January 2006 through December 2011. High-risk features included age <40 years, multifocality/multicentricity, lymphovascular invasion, medial/central tumor location, and high nuclear grade. RESULTS: Among 672 eligible patients, only 15 received PMRT and were excluded. Of the remaining 657 patients, 187 (28%) had 1 high-risk feature and 449 patients (68%) had ≥ 2 high-risk features. A total of 36 patients with unknown tumor grade were excluded from risk analysis. Approximately 98% of patients underwent sentinel lymph node biopsy alone and 86% received adjuvant systemic therapy. At a median of 5.6 years of follow-up, the locoregional disease recurrence (LRR) rate was 4.7% (31 patients). Increasing tumor size was found to be associated with LRR (hazard ratio, 1.70; P = .006), whereas other high-risk features were not (all P > .05). Receipt of systemic therapy decreased the LRR rate (hazard ratio, 0.40; P = .03). Although crude LRR rates increased from 3.8% to 9.4% with 1 versus ≥ 4 high-risk features, the number of risk factors was not found to be significantly associated with LRR (P = .54). CONCLUSIONS: In the current study, a low crude LRR rate (4.7%) was observed in a large unselected cohort of patients with T1 to T2N0 breast cancer with high-risk features who were treated with mastectomy and systemic therapy without PMRT. Although increasing tumor size and the omission of systemic therapy were found to be predictive, other features did not confer a higher LRR risk either independently or together, and do not by themselves mandate the use of PMRT in this patient population. Cancer 2017;123:2626-33. © 2017 American Cancer Society.

Axillary Dissection and Nodal Irradiation Can Be Avoided for Most Node-positive Z0011-eligible Breast Cancers: A Prospective Validation Study of 793 Patients.

OBJECTIVE: To determine rates of axillary dissection (ALND) and nodal recurrence in patients eligible for ACOSOG Z0011. BACKGROUND: Z0011 demonstrated that patients with cT1-2N0 breast cancers and 1 to 2 involved sentinel lymph nodes (SLNs) having breast-conserving therapy 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 Z0011 had 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 August 2010 to December 2016, 793 patients met Z0011 eligibility criteria and had SLN metastases. Among them, 130 (16%) had ALND; ALND did not vary based on age, estrogen receptor, progesterone receptor, or HER2 status. Five-year event-free survival after SLN alone was 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.