The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database (NCDB).

PURPOSE: Primary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer. METHODS: The National Cancer Database (NCDB, 2010-2016) was queried for patients with stage IV HR-positive, HER2-negative invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). We compared clinicopathologic features, primary site surgery rates, and outcomes by histologic subtype. Multivariable Cox proportional hazard models with and without propensity score matching were used for overall survival (OS) analyses. RESULTS: In 25,294 patients, primary site surgery was slightly but significantly less common in the 6,123 patients with ILC compared to the 19,171 patients with IDC (26.9% versus 28.8%, p = 0.004). Those with ILC were less likely to receive chemotherapy (41.3% versus 47.4%, p < 0.0001) or radiotherapy (29.1% versus 37.9%, p < 0.0001), and had shorter OS. While mastectomy rates were similar, those with ILC who underwent lumpectomy had significantly higher positive margin rates (ILC 15.7% versus IDC 11.2%, p = 0.025). In both groups, the odds of undergoing surgery decreased over time, and were higher in younger patients with T2/T3 tumors and higher nodal burden. CONCLUSION: Lobular histology is associated with less primary site surgery, higher positive margin rates, less radiotherapy and chemotherapy, and shorter OS compared to those with HR-positive HER2-negative IDC. These findings support the need for ILC-specific data and treatment approaches in the setting of metastatic disease.

[A Long-Surviving Case of Locally Advanced Breast Cancer with Multiple Lung Metastasis].

We report a case of right advanced breast cancer with multiple lung metastases in a 66-year-old woman. Her breast cancer( invasive ductal carcinoma, cT4bN1M1, Stage Ⅳ)was resected in October 2007(mastectomy plus axillary lymph node dissection)after local arterial infusion therapy(total dose 5-FU 4,735 mg plus adriamycin 180 mg), which caused bilateral lung arterial embolism due to deep vein thrombosis in right her leg. She had to be treated by anticoagulant therapy, mechanical ventilation and placement of IVC filter before her operation. Subsequent chemo-endocrine therapy(docetaxel 6 courses plus anastrozole)was continued. In October 2008, a CT scan showed disappearance of multiple lung metastases (complete response). In November 2015 (8 years after her operation), a CT scan showed recurrence of multiple lung metastases and endocrine therapy was changed to tamoxifen. A year later, a CT scan showed disappearance of multiple lung metastases(complete response)again and keep a condition of complete response in her breast cancer until May 2023 (15 years after her operation).

Clinical characteristics and treatment outcomes of invasive ductal and lobular carcinoma: analyses of 54,832 taiwan cancer registry index cases.

PURPOSE: Invasive lobular cancer (ILC) is the second most common histology type of breast cancer followed by invasive ductal carcinoma (IDC). This study aimed to investigate the characteristic, treatment strategies, and clinical outcomes of ILC based on a national population-based cancer registry. METHODS: This study recruited 2671 ILC and 52,215 IDC patients diagnosed between 2011 and 2017 using the Taiwan Cancer Registry (TCR). Correlations between ILC and IDC subgroups were assessed using 1:4 propensity score matching and compared using the χ2 test. Disease free survival(DFS) and overall survival(OS) were estimated using the Kaplan-Meier method with the log-rank test. The risk of disease relapse and mortality were assessed using Cox proportional hazards model. RESULTS: ILC patients had larger tumor sizes, more positive axillary lymph node involvement, lower tumor grade, and higher cancer stage than IDC patients. After matching, ILC patients had a significantly higher rate of receiving mastectomy (58.93% and 53.85%) and positive surgical margin regardless of surgery type. ILC exhibited a significantly higher rate of distant metastasis than IDC(3.67% and 2.93%), but no difference in local recurrence rate, DFS or OS between the two groups. Higher cancer stage, higher grade, and mastectomy were risk factors for disease relapse and cancer-specific mortality. The hormone receptor-positive and HER2 over-expression subtypes were found to be associated with a reduced risk of disease relapse, while only PR positivity was associated with a decreased risk of mortality. (all P-values < 0.05). CONCLUSION: ILC patients had a higher mastectomy rate, higher surgical margin rate and distant metastasis rate than IDC patients. There is no significant difference in DFS or OS between ILC and IDC patients. Mastectomy was associated with poor outcomes regardless of ILC or IDC.

Prediction of nipple involvement in breast cancer after neoadjuvant chemotherapy: Should we rely on breast MRI to preserve the nipple?

BACKGROUND: Indications for nipple sparing mastectomy (NSM) is extending to post-neoadjuvant chemotherapy (NAC) setting. Eligibility for NSM with an optimum tumor-nipple distance (TND) after NAC is unclear. We examined predictive factors for nipple tumor involvement in patients undergoing total mastectomy following NAC. METHODS: Clinical and pathological data from prospectively collected medical records of women with invasive breast carcinoma, who were undergone NAC and total mastectomy with sentinel lymph node biopsy and/or axillary lymph node dissection were analyzed. PreNAC and postNAC magnetic resonance imaging (MRI) views were examined and a cut-off TND value for predicting the negative nipple tumor status was determined. RESULTS: Among 180 women, the final mastectomy specimen analysis revealed that 12 (7%) had nipple involvement as invasive carcinoma. Patients with nipple involvement had more postNAC multifocal/multicentric tumors (p: 0.03), larger tumors on preNAC and postNAC images (p: 0.002 and p < 0.001), shorter median TNDs on preNAC and postNAC images (7 mm-IQR 1.5-14, p: 0.005 and 8.5 mm-IQR 3-15.5, p < 0.001, respectively), more nipple retraction on preNAC and postNAC images (p: 0.007 and p: 0.006) and more nipple areola complex skin thickening (> 2mm) on preNAC and postNAC images (p < 0.001 and p: 0.01). The best likelihood ratios (LR) belonged to the postNAC positivity of the < 20 mm TND, with a + LR of 3.40, and - LR of 0.11 for nipple involvement. PreNAC positivity of the < 20 mm TND also had a similar - LR of 0.14. CONCLUSION: A TND-cut-off  ≥ 2 cm on preNAC and postNAC MRI was shown to be highly predictive of negative nipple tumor involvement.

Successful Breast Conservation After Neoadjuvant Chemotherapy in Lobular Breast Cancer: The Role of Menopausal Status in Response to Treatment.

BACKGROUND: While neoadjuvant chemotherapy (NAC) has been shown to increase rates of breast conservation surgery (BCS) for breast cancer, response rates in invasive lobular carcinoma (ILC) appear lower than other histologic subtypes. Some data suggest higher response rates to NAC in premenopausal versus postmenopausal patients, but this has not been studied in ILC. We evaluated the rates of successful BCS after NAC in patients with ILC stratified by menopausal status. PATIENTS AND METHODS: We analyzed data from a single-institution cohort of 666 patients with stage I-III hormone receptor positive HER-2 negative ILC. We used t-tests, chi-squared tests, and multivariable logistic regression to investigate rates of NAC use, attempted BCS, and associations between NAC and successful BCS by menopausal status. RESULTS: In 217 premenopausal and 449 postmenopausal patients, NAC was used more often in the premenopausal group (15.2% vs. 9.8%, respectively, p = 0.041). Among those who attempted breast conservation (51.3% of pre- and 64.8% of postmenopausal cohorts), NAC was not associated with successful BCS in either group. Interestingly, for postmenopausal patients, receipt of NAC was significantly associated with increased rates of completion mastectomy in those who had positive margins at the first attempt at BCS. CONCLUSION: NAC was not associated with successful BCS in either premenopausal or postmenopausal patients with ILC. Although premenopausal patients were more likely to receive NAC, these data suggest that menopausal status may not be a good predictor of response to chemotherapy. Better predictors of response and more efficacious treatment for patients with ILC are needed.

Expression-Based Diagnosis, Treatment Selection, and Drug Development for Breast Cancer.

There is currently no gene expression assay that can assess if premalignant lesions will develop into invasive breast cancer. This study sought to identify biomarkers for selecting patients with a high potential for developing invasive carcinoma in the breast with normal histology, benign lesions, or premalignant lesions. A set of 26-gene mRNA expression profiles were used to identify invasive ductal carcinomas from histologically normal tissue and benign lesions and to select those with a higher potential for future cancer development (ADHC) in the breast associated with atypical ductal hyperplasia (ADH). The expression-defined model achieved an overall accuracy of 94.05% (AUC = 0.96) in classifying invasive ductal carcinomas from histologically normal tissue and benign lesions (n = 185). This gene signature classified cancer development in ADH tissues with an overall accuracy of 100% (n = 8). The mRNA expression patterns of these 26 genes were validated using RT-PCR analyses of independent tissue samples (n = 77) and blood samples (n = 48). The protein expression of PBX2 and RAD52 assessed with immunohistochemistry were prognostic of breast cancer survival outcomes. This signature provided significant prognostic stratification in The Cancer Genome Atlas breast cancer patients (n = 1100), as well as basal-like and luminal A subtypes, and was associated with distinct immune infiltration and activities. The mRNA and protein expression of the 26 genes was associated with sensitivity or resistance to 18 NCCN-recommended drugs for treating breast cancer. Eleven genes had significant proliferative potential in CRISPR-Cas9/RNAi screening. Based on this gene expression signature, the VEGFR inhibitor ZM-306416 was discovered as a new drug for treating breast cancer.

[A Case of Multicentric HER2-Positive Breast Cancer with Alterations of the Intrinsic Subtype].

In cases where there are 2 or more tumors, it is crucial to conduct core needle biopsies on each of them. A 39-year-old woman presented at our hospital with pain in her left breast. Ultrasonography(US)revealed the presence of 2 contiguous tumors: a 35 mm tumor(tumor 1)and a 20 mm tumor(tumor 2)in the AC area of the left breast. US-guided core needle biopsies(CNB)were performed. The histological findings confirmed an invasive ductal carcinoma, characterized by ER(-)/ PR(-)/HER2(3+). Neoadjuvant chemotherapy indicated tumor 1 as PD and tumor 2 as PR, and surgery was subsequently performed(Bt plus SLN). Upon histopathological examination, the findings demonstrated a non-pCR invasive ductal carcinoma, featuring an ER(+)/PR(-)/HER2(-)profile. Depending on the specific subtype identified, post-operative treatment included HER2-targeted therapy or ER/PR-targeting hormone therapy in conjunction with chemotherapy.

Adjuvant chemotherapy in patients with invasive lobular carcinoma and use of the 21-gene recurrence score: A National Cancer Database analysis.

BACKGROUND: Invasive lobular carcinoma (ILC) is traditionally considered less responsive to chemotherapy. Although the Oncotype recurrence score (RS) has been validated to identify high-risk patients who benefit from chemotherapy, some studies have questioned its relevance in patients with ILC. The objective of this study was to better characterize potential use of the RS in these patients. METHODS: The National Cancer Database was used to identify women with stage I through III, T1 through T3, N0 or N1, hormone receptor-positive, HER2-negative ILC or invasive ductal carcinoma (IDC) who had an available RS between 2010 and 2016. Multivariable Cox regression was used to model the effect of variables on 5-year overall survival (OS). The Kaplan-Meier method was used to estimate OS according to the RS, nodal status, and chemotherapy. RESULTS: In total, 15,763 patients with ILC and 100,070 with IDC were identified. The mean age of patients with ILC and IDC was 59.2 ± 9.1 and 57.2 ± 9.8, respectively. A lower percentage of patients with ILC versus those with IDC had a high RS, defined as >25 (6.6% vs 16.0%; P < .0001). ILC patients with a high RS who had N0 or N1 disease received approximately 10% less chemotherapy compared with similar patients who had IDC. The results indicated that the RS had statistically significant prognostic value for patients with ILC. In addition, an absolute OS advantage was correlated with the receipt of chemotherapy by patients with ILC who had a high RS with N0 or N1 disease. CONCLUSIONS: Patients with ILC who have a high RS are treated less often with chemotherapy compared with similar patients who have IDC. Nevertheless, the RS has a prognostic as well as a predictive value in ILC, with an association between OS benefit and chemotherapy receipt in patients who have ILC with a high RS, especially if they have N1 disease. LAY SUMMARY: Invasive lobular carcinoma (ILC) is a subtype of breast cancer comprising about 15% of cases. The Oncotype recurrence score (RS) is a genetic test of breast tumors that helps predict which patients might benefit from chemotherapy. Some have doubted the relevance of the RS for patients with ILC. In this study, the authors show that the RS is relevant for patients who have ILC. The RS has the potential of predicting the risk of recurrence and identifying patients with ILC who might benefit from chemotherapy.

Prognosis and effectiveness of chemotherapy for medullary breast carcinoma.

PURPOSE: We aimed to determine the prognosis and potential benefit of postoperative chemotherapy according to subtype of medullary breast carcinoma (MedBC), a very rare invasive breast cancer. METHODS: A cohort of 1518 female patients with unilateral MedBC and 284,544 invasive ductal carcinoma (IDC) cases were enrolled from the Japanese Breast Cancer Registry. Prognosis of MedBC was compared to IDC among patients with estrogen receptor (ER)-negative and HER2-negative subtype (553 exact-matched patients) and ER-positive and HER2-negative subtype (163 MedBC and 489 IDC patients via Cox regression). Disease free-survival (DFS) and overall survival (OS) were compared between propensity score-matched adjuvant chemotherapy users and non-users with ER-negative and HER2-negative MedBC. RESULTS: Among ER-negative and HER2-negative subtype patients, DFS (hazard ratio (HR) 0.45; 95% confidence interval (95% CI), 0.30-0.68; log-rank P < 0.001) and OS (HR 0.51; 95% CI 0.32-0.83; log-rank P = 0.004) were significantly better in MedBC than IDC. Patients treated with postoperative chemotherapy showed better DFS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) and OS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) compared to those without. For the ER-positive and HER2-negative subtype, the point estimate for HR for DFS was 0.60 (95% CI 0.24-1.22) while that for OS was 0.98 (95% CI 0.46-1.84) for MedBC. CONCLUSION: In ER-negative and HER2-negative MedBC, the risk of recurrence and death was significantly lower than that of IDC, about half. Postoperative chemotherapy reduced recurrence and mortality. ER-positive and HER2-negative MedBC may have a lower risk of recurrence compared to IDC.

Neoadjuvant Endocrine Therapy and Delays in Surgery for Ductal Carcinoma in Situ: Implications for the Coronavirus Pandemic.

BACKGROUND: Surgical delays are associated with invasive cancer for patients with ductal carcinoma in situ (DCIS). During the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pandemic, neoadjuvant endocrine therapy (NET) was used as a bridge until postponed surgeries resumed. This study sought to determine the impact of NET on the rate of invasive cancer for patients with a diagnosis of DCIS who have a surgical delay compared with those not treated with NET. METHODS: Using the National Cancer Database, the study identified women with hormone receptor-positive (HR+) DCIS. The presence of invasion on final pathology was evaluated after stratifying by receipt of NET and by intervals based on time from diagnosis to surgery (≤30, 31-60, 61-90, 91-120, or 121-365 days). RESULTS: Of 109,990 women identified with HR+ DCIS, 276 (0.3%) underwent NET. The mean duration of NET was 74.4 days. The overall unadjusted rate of invasive cancer was similar between those who received NET ((15.6%) and those who did not (12.3%) (p = 0.10). In the multivariable analysis, neither the use nor the duration of NET were independently associated with invasion, but the trend across time-to-surgery categories demonstrated a higher rate of upgrade to invasive cancer in the no-NET group (p < 0.001), but not in the NET group (p = 0.97). CONCLUSIONS: This analysis of a pre-COVID cohort showed evidence for a protective effect of NET in HR+ DCIS against the development of invasive cancer as the preoperative delay increased, although an appropriately powered prospective trial is needed for a definitive answer.

Is Nodal Clipping Beneficial for Node-Positive Breast Cancer Patients Receiving Neoadjuvant Chemotherapy?

BACKGROUND: In cN1 patients rendered cN0 with neoadjuvant chemotherapy, the false-negative rate of sentinel lymph node biopsy (SLNB) is < 10% when ≥ 3 sentinel lymph nodes (SLNs) are removed. The added value of nodal clipping in this scenario is unknown. Here we determine how often the clipped node is a sentinel node when ≥ 3 SLNs are retrieved. METHODS: We identified cT1-3N1 patients treated between 02/2018 and 10/2021 with a clipped lymph node at presentation. SLNB was performed with a standardized approach of dual-tracer mapping and retrieval of ≥ 3 SLNs. Clipped nodes were not localized; SLNs were X-rayed intraoperatively to determine clip location. Axillary lymph node dissection (ALND) was performed for any residual disease or retrieval of < 3 SLNs. RESULTS: Of 269 patients, 251 (93%) had ≥ 3 SLNs. Median age was 51 years; the majority (92%) had ductal histology; 46% were HR+/HER2-. The median number of SLNs removed was 4 (IQR 3,5). The clipped node was an SLN in 88% (220/251) of cases. Of the 31 where the clipped node was not, 13 had a positive SLN mandating ALND, and the clip was identified in the ALND specimen. In the remaining 18, where ≥ 3 negative SLNs were retrieved and an ALND was not performed, the clip was not retrieved, with no axillary failures in this group (median follow-up: 55 months). CONCLUSION: When the SLNB procedure is optimized with dual tracer and retrieval of ≥ 3 SLNs, the clipped node is an SLN in the majority of cases, suggesting that failure to retrieve the clipped node should not be an indication for ALND.

Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma-A Histopathological Study.

Background and Objectives: Breast cancer (BC) is the first diagnosed type of cancer and the second leading cause of cancer-related mortality in women. In addition, despite the improvement in treatment and survival in these patients, the global prevalence and incidence of this cancer are rising, and its mortality may be different according to the histological subtype. Invasive lobular carcinoma (ILC) is less common but entails a poorer prognosis than infiltrative ductal carcinoma (IDC), exhibiting a different clinical and histopathological profile. Deepening study on the molecular profile of both types of cancer may be of great aid to understand the carcinogenesis and progression of BC. In this sense, the aim of the present study was to explore the histological expression of Insulin receptor substrate 4 (IRS-4), cyclooxygenase 2 (COX-2), Cyclin D1 and retinoblastoma protein 1 (Rb1) in patients with ILC and IDC. Patients and Methods: Thus, breast tissue samples from 45 patients with ILC and from 45 subjects with IDC were analyzed in our study. Results: Interestingly, we observed that IRS-4, COX-2, Rb1 and Cyclin D1 were overexpressed in patients with ILC in comparison to IDC. Conclusions: These results may indicate a differential molecular profile between both types of tumors, which may explain the clinical differences among ILC and IDC. Further studies are warranted in order to shed light onto the molecular and translational implications of these components, also aiding to develop a possible targeted therapy to improve the clinical management of these patients.

Pregnancy after breast cancer: Results from a prospective cohort of young women with breast cancer.

BACKGROUND: Many young women with newly diagnosed breast cancer are interested in future pregnancies. Prospective data regarding fertility interest and reproductive patterns after diagnosis are needed to counsel patients. METHODS: The Young Women's Breast Cancer Study is a multicenter, prospective cohort of women who were diagnosed with breast cancer at age ≤40 years between 2006 and 2016. Women complete surveys at baseline, every 6 months for 3 years, then annually. Here, the authors describe fertility interest and pregnancies within 5 years of diagnosis for women with stage 0 through III breast cancer. RESULTS: Of 1026 eligible participants, 368 (36%) reported interest in future biologic children at least once within 5 years after diagnosis, including 16% at 5 years after diagnosis. Among 130 women who attempted to become pregnant, 90 (69.2%) conceived; and, among 896 women who did not attempt to conceive, 18 (2.0%) became pregnant, with a total of 152 pregnancies resulting in 91 live births. Factors associated with pregnancy included younger versus older age at diagnosis (aged ≤30 vs 36-40 years: odds ratio [OR], 6.63; 95% CI, 3.18-13.83; P < .0001; aged 31-35 vs 36-40 years: OR, 5.86; 95% CI, 3.37-10.17; P < .0001) and being nulliparous versus parous (OR, 2.66; 95% CI, 1.56-4.53; P = .001). The receipt of endocrine therapy versus no endocrine therapy (OR, 0.35; 95% CI, 0.20-0.59; P = .001) was inversely associated with pregnancy. CONCLUSIONS: Many women remain interested in future fertility in the 4 years after a breast cancer diagnosis, indicating that longitudinal fertility discussions are needed. Although a minority of those interested in having children attempted to become pregnant in the first 5 years, most who attempted to conceive did so and had live births.

Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial.

BACKGROUND: Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase inhibitors (MAP.3 and International Breast Cancer Intervention Study II [IBIS-II]). Here, we report blinded long-term follow-up results for the IBIS-II trial, which compared anastrozole with placebo, with the objective of determining the efficacy of anastrozole for preventing breast cancer (both invasive and ductal carcinoma in situ) in the post-treatment period. METHODS: IBIS-II is an international, randomised, double-blind, placebo-controlled trial. Postmenopausal women at increased risk of developing breast cancer were recruited and were randomly assigned (1:1) to either anastrozole (1 mg per day, oral) or matching placebo daily for 5 years. After treatment completion, women were followed on a yearly basis to collect data on breast cancer incidence, death, other cancers, and major adverse events (cardiovascular events and fractures). The primary outcome was all breast cancer. FINDINGS: 3864 women were recruited between Feb 2, 2003, and Jan 31, 2012. 1920 women were randomly assigned to 5 years anastrozole and 1944 to placebo. After a median follow-up of 131 months (IQR 105-156), a 49% reduction in breast cancer was observed for anastrozole (85 vs 165 cases, hazard ratio [HR] 0·51, 95% CI 0·39-0·66, p<0·0001). The reduction was larger in the first 5 years (35 vs 89, 0·39, 0·27-0·58, p<0·0001), but still significant after 5 years (50 vs 76 new cases, 0·64, 0·45-0·91, p=0·014), and not significantly different from the first 5 years (p=0·087). Invasive oestrogen receptor-positive breast cancer was reduced by 54% (HR 0·46, 95% CI 0·33-0·65, p<0·0001), with a continued significant effect in the period after treatment. A 59% reduction in ductal carcinoma in situ was observed (0·41, 0·22-0·79, p=0·0081), especially in participants known to be oestrogen receptor-positive (0·22, 0·78-0·65, p<0·0001). No significant difference in deaths was observed overall (69 vs 70, HR 0·96, 95% CI 0·69-1·34, p=0·82) or for breast cancer (two anastrozole vs three placebo). A significant decrease in non-breast cancers was observed for anastrozole (147 vs 200, odds ratio 0·72, 95% CI 0·57-0·91, p=0·0042), owing primarily to non-melanoma skin cancer. No excess of fractures or cardiovascular disease was observed. INTERPRETATION: This analysis has identified a significant continuing reduction in breast cancer with anastrozole in the post-treatment follow-up period, with no evidence of new late side-effects. Further follow-up is needed to assess the effect on breast cancer mortality. FUNDING: Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, Sanofi Aventis, and AstraZeneca.

Clinico-pathologic predictors of patterns of residual disease following neoadjuvant chemotherapy for breast cancer.

Among breast cancer patients treated with neoadjuvant chemotherapy (NAC) who do not experience a pathologic complete response (pCR), the pattern of residual disease in the breast varies. Pre-treatment clinico-pathologic features that predict the pattern of residual tumor are not well established. To investigate this issue, we performed a detailed review of histologic sections of the post-treatment surgical specimens for 665 patients with stage I-III breast cancer treated with NAC followed by surgery from 2004 to 2014 and for whom slides of the post-NAC surgical specimen were available for review. This included 242 (36.4%) patients with hormone receptor (HR)+/HER2- cancers, 216 (32.5%) with HER2+ tumors, and 207 (31.1%) with triple negative breast cancer (TNBC). Slide review was blinded to pre-treatment clinico-pathologic features. pCR was achieved in 7.9%, 37.0%, and 37.7%, of HR+/HER2- cancers, HER2+ cancers, and TNBC respectively (p < 0.001). Among 389 patients with residual invasive cancer in whom the pattern of residual disease could be assessed, 287 (73.8%) had a scattered pattern and 102 (26.2%) had a circumscribed pattern. In both univariate and multivariate analyses, there was a significant association between tumor subtype and pattern of response. Among patients with HR+/HER2- tumors, 89.4% had a scattered pattern and only 10.6% had a circumscribed pattern. In contrast, among those with TNBC 52.8% had a circumscribed pattern and 47.2% had a scattered pattern (p < 0.001). In addition to subtype, histologic grade and tumor size at presentation were also significantly related to the pattern of residual disease in multivariate analysis, with lower grade and larger size each associated with a scattered response pattern (p = 0.002 and p = 0.01, respectively). A better understanding of the relationship between pre-treatment clinico-pathologic features of the tumor and pattern of residual disease may be of value for helping to guide post-chemotherapy surgical management.

Changes in Management Strategy and Impact of Neoadjuvant Therapy on Extent of Surgery in Invasive Lobular Carcinoma of the Breast: Analysis of the National Cancer Database (NCDB).

BACKGROUND: Given reports of low response rates to neoadjuvant chemotherapy (NAC) in invasive lobular carcinoma (ILC), we evaluated whether use of alternative strategies such as neoadjuvant endocrine therapy (NET) is increasing. Additionally, we investigated whether NET is associated with more breast conservation surgery (BCS) and less extensive axillary surgery in those with ILC. PATIENTS AND METHODS: We queried the NCDB from 2010 to 2016 and identified all women with stage I-III hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) ILC who underwent surgery. We used Cochrane-Armitage tests to evaluate trends in utilization of the following treatment strategies: NAC, short-course NET, long-course NET, and primary surgery. We compared rates of BCS and extent of axillary surgery stratified by clinical stage and tumor receptor subtype for each treatment strategy. RESULTS: Among 69,312 cases of HR+/HER2- ILC, NAC use decreased slightly (from 4.7 to 4.2%, p = 0.007), while there was a small but significant increase in long-course NET (from 1.6 to 2.7%, p < 0.001). Long-course NET was significantly associated with increased BCS in patients with cT2-cT4 disease and less extensive axillary surgery in clinically node positive patients with HR+/HER2- tumors. CONCLUSIONS: Primary surgery remains the most common treatment strategy in patients with ILC. However, NAC use decreased slightly over the study period, while the use of long-course NET had a small increase and was associated with more BCS and less extensive axillary surgery.

Margin Assessment and Re-excision Rates for Patients Who Have Neoadjuvant Chemotherapy and Breast-Conserving Surgery.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has enabled more patients to be eligible for breast-conservation surgery (BCS). Achieving negative lumpectomy margins, however, is challenging due to changes in tissue composition and potentially scattered residual carcinoma in the tumor bed. Data regarding BCS after NAC have shown variable re-excision rates. MarginProbe (Dilon Technologies, Newport News, VA, USA) has been shown to identify positive resection margins intraoperatively and to reduce the number of re-excisions in primary BCS, but has not been studied in NAC+BCS cases. This study aimed to investigate the clinicopathologic characteristics, margin status, and re-excision rates for NAC+BCS patients with and without the use of MarginProbe. METHODS: The Institutional Breast Cancer Database was queried for patients who received NAC and had BCS from 2010 to 2019. The variables of interest were demographics, tumor characteristics, pathologic complete response (pCR), MarginProbe use, and re-excision rates. RESULTS: The study population consisted of 214 patients who had NAC, 61 (28.5 %) of whom had NAC+BCS. The median age of the patients was 53.5 years. A pCR was achieved for 19 of the patients (31.1 %). Of the remaining 42 patients, 9 (21 %) had close or positive margins that required re-excision. Re-excision was associated with a larger residual tumor size (p = 0.025) and estrogen receptor (ER)-positive disease before NAC (p = 0.041). MarginProbe use was associated with a lower re-excision rate for the patients who had NAC+BCS (6 % vs. 31 %, respectively). CONCLUSION: The patients with a larger residual tumor burden and ER-positive disease had a greater risk for inadequate margins at surgery. MarginProbe use was associated with a lower re-excision rate. Techniques to reduce the need for re-excision will support the use of BCS after NAC.

Loss of HER2-positivity following neoadjuvant targeted therapy for breast cancer is not associated with inferior oncologic outcomes.

BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are treated with trastuzumab-based neoadjuvant therapy (NAT); some patients with residual disease post-NAT show loss of HER2 amplification and has been inconsistently associated with oncologic outcomes. METHODS: We queried our multi-institutional cancer registry for women with HER2-positive breast cancer undergoing NAT from 2011 to 2018. Clinicopathologic, treatment-related, and outcomes data were collected. Kaplan-Meier and Cox proportional hazards analysis were used to evaluate oncologic outcomes. RESULTS: A total of 348 patients were identified; 166 (48%) had a pathologic complete response. Of the 182 patients with residual disease, 87 (48%) were HER2-positive, 34 (19%) were HER2-negative, and 61 (33%) were HER2-unknown, with a median follow-up of 44 months. There were no factors associated with HER2 loss apart from age. On Kaplan-Meier analysis, estimated 5-year recurrence-free survival (RFS) and overall survival (OS) for patients with HER2-positive residual disease was 81% and 92%, respectively, and 74% (log rank p = 0.75) and 81% (p = 0.35) in patients with HER2-negative residual disease. CONCLUSION: The loss of HER2-positivity following NAT is not associated with worse 5-year RFS or OS. We do not recommend retesting HER2 status following NAT for the purpose of clinical management; these patients should complete targeted adjuvant therapy.

Leveraging the increased rates of pathologic complete response after neoadjuvant treatment in breast cancer to de-escalate surgical treatments.

INTRODUCTION: Breast conservative surgery (BCS) and sentinel lymph node biopsy (SLNB) after neoadjuvant treatment (NAT) is safe and effective for selected patients. This aim of this study is to evaluate the impact of anatomic site of response on outcomes and to assess the real population who may benefit from nonsurgical approaches after NAT. MATERIAL AND METHODS: From a prospectively maintained database, patients with T1-4 N0-2 breast cancer undergoing NAT were identified. Clinicopathological and survival rates were compared in relation to response and anatomic site of response. RESULTS: Six hundred and forty-six patients were included in the study. Pathologic complete response (pCR) was an independent factor for BCS and SLN. HER2 positive and TN tumors with cN0 achieving a breast pCR remain ypN0 (p = .002). Residual axillary disease was associated with breast residual tumor (p = .05) and subtype (p = .001). With a median follow up of 35.25 months, patients with any pCR had improved survival when compared with partial response, but not significant differences between pCR, axillary pCR, or breast pCR. CONCLUSION: Achieving a pCR increases BCS and SLN. In selected subgroups, sparing any axillary surgery after NAT maybe feasible. In cN+ patients, any pCR was associated with survival, but not the anatomic site of response.

Evaluating the effect of neoadjuvant chemotherapy on surgical outcomes after breast conserving surgery.

BACKGROUND: Neoadjuvant chemotherapy (NAC) increases breast-conserving surgery (BCS) rates with comparable locoregional control and survival outcomes to adjuvant therapy. More women are receiving NAC and achieving pathologic complete responses (pCR). This study sought to evaluate the effect of NAC on surgical outcomes after the adoption of a "no-ink-on-tumor" margin policy in patients undergoing primary BCS (PBSC). METHODS: An IRB approved database was queried for women undergoing BCS for invasive breast cancer after March 2014. We compared patients who underwent NAC followed by BCS versus PBCS. Demographic, tumor, treatment, and outcome variables were compared using both univariate and multivariable analysis. RESULTS: A total of 162 patients were evaluated. NAC patients had significantly lower re-excision rates (0% NAC vs. 9% PBCS, p = .03), margin positivity (0% NAC vs. 5% PBCS, p = .01), and greater patient satisfaction with breast cosmesis (97 NAC vs. 77 PBCS, p = .01). On multivariable analysis, NAC was not an independent predictor of lower final resection volume, total complications, or greater satisfaction with breasts when controlling for age and T category at diagnosis. CONCLUSION: NAC followed by BCS may offer less margin positivity, lower re-excision rates, and greater patient satisfaction when compared to a contemporary PBCS cohort in the "no-ink-on-tumor" era.