Locally Advanced Breast Cancer Research Articles

Examination of Tumor Regression Grading Systems in Breast Cancer Patients Who Received Neoadjuvant Therapy

Neoadjuvant therapy is a common form of treatment in locally advanced breast cancer (LABC) patients. Besides some guidelines for grading regression, a standardized general scheme is not yet available. The aim of our study was to compare the prognostic impact of different regression grading systems, namely the TR/NR, Chevallier, Sataloff, Denkert-Sinn, Miller-Payne, NSABP-B18, Residual Disease in Breast and Nodes and Residual Cancer Burden (RCB) on disease-free (DFS) and overall survival (OS). Data of 746 breast cancer patients treated in neoadjuvant setting between 1999 and 2019 have been included. The different regression grades and follow-up data were collected from medical charts. Statistical analysis included the Kaplan-Meier method, log-rank test and multivariate Cox regression. The average patient age was 55 years. The DFS and OS estimates of patients with complete pathological regression and residual in situ carcinoma have been significantly more favorable than those having partial regression or no signs of regression (pDFS<0.001, pOS < 0.001). Significant differences were found between DFS estimates of classes with partial regression and without regression defined by RCB. Concerning DFS estimates, the RCB classification (p = 0.019), while regarding OS data the y-stage (p = 0.011) and the nodal status (ypN; p = 0.045) were significant prognosticators by multivariate Cox regression. Regression grading systems help the evaluation of regression in LABC patients treated with neoadjuvant therapy. Of the several grading systems compared, the RCB classification makes the best distinction between the outcomes of the different classes, therefore we recommend the inclusion of RCB into the histopathological findings.

A priori prediction of tumour response to neoadjuvant chemotherapy in breast cancer patients using quantitative CT and machine learning

Response to Neoadjuvant chemotherapy (NAC) has demonstrated a high correlation to survival in locally advanced breast cancer (LABC) patients. An early prediction of responsiveness to NAC could facilitate treatment adjustments on an individual patient basis that would be expected to improve treatment outcomes and patient survival. This study investigated, for the first time, the efficacy of quantitative computed tomography (qCT) parametric imaging to characterize intra-tumour heterogeneity and its application in predicting tumour response to NAC in LABC patients. Textural analyses were performed on CT images acquired from 72 patients before the start of chemotherapy to determine quantitative features of intra-tumour heterogeneity. The best feature subset for response prediction was selected through a sequential feature selection with bootstrap 0.632 + area under the receiver operating characteristic (ROC) curve ({mathrm{A}mathrm{U}mathrm{C}}_{0.632+}) as a performance criterion. Several classifiers were evaluated for response prediction using the selected feature subset. Amongst the applied classifiers an Adaboost decision tree provided the best results with cross-validated {mathrm{A}mathrm{U}mathrm{C}}_{0.632+}, accuracy, sensitivity and specificity of 0.89, 84%, 80% and 88%, respectively. The promising results obtained in this study demonstrate the potential of the proposed biomarkers to be used as predictors of LABC tumour response to NAC prior to the start of treatment.

Quantitative ultrasound radiomics in predicting response to neoadjuvant chemotherapy in patients with locally advanced breast cancer: Results from multi-institutional study.

BackgroundThis study was conducted in order to develop a model for predicting response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC) using pretreatment quantitative ultrasound (QUS) radiomics.MethodsThis was a multicenter study involving four sites across North America, and appropriate approval was obtained from the individual ethics committees. Eighty‐two patients with LABC were included for final analysis. Primary tumors were scanned using a clinical ultrasound system before NAC was started. The tumors were contoured, and radiofrequency data were acquired and processed from whole tumor regions of interest. QUS spectral parameters were derived from the normalized power spectrum, and texture analysis was performed based on six QUS features using a gray level co‐occurrence matrix. Patients were divided into responder or nonresponder classes based on their clinical‐pathological response. Classification analysis was performed using machine learning algorithms, which were trained to optimize classification accuracy. Cross‐validation was performed using a leave‐one‐out cross‐validation method.ResultsBased on the clinical outcomes of NAC treatment, there were 48 responders and 34 nonresponders. A K‐nearest neighbors (K‐NN) approach resulted in the best classifier performance, with a sensitivity of 91%, a specificity of 83%, and an accuracy of 87%.ConclusionQUS‐based radiomics can predict response to NAC based on pretreatment features with acceptable accuracy.

Effects of Neo-Adjuvant Chemotherapy on CD8 + Serum Levels in Local Advanced Stage Breast Cancer Patients

Introduction.CD8 + CTLs are important components of tumor specific cellular adaptive immunity in breast cancer. Chemotherapy can increase the response of cytotoxic lymphocytes and provide anti-tumor immunity. Therefore, chemotherapy can cause cell death and trigger tumor antigens that are processed by APC and activate CD8 + cells to destroy tumor cells. Evaluation of the immune system before treatment can predict chemotherapy response. The purpose of this study was to assess the effect of neo-adjuvant chemotherapy on serum CD8 + levels in patients with locally advanced breast cancer.Methods.Non-comparative clinical trials were conducted at Dr. Mohammad Hoesin Hospital Palembang from October 2017 to June 2018.The sample of this study was 30 breast cancer patients who met the inclusion criteria. All samples underwent FAC neo-adjuvant chemotherapy and data were analyzed with SPSS version 21. Results.The mean age of advanced breast cancer patients was 45.97 ± 10,526 years with an age range of 30-66 years. Serum CD8 + levels after chemotherapy decreased significantly compared to before chemotherapy (p = 0.000). The value of serum CD8 + before chemotherapy has a sensitivity of 42.86% and specificity of 43.48% with a cut of point of 660.7 cells / mm3.Conclusion.Neo-adjuvant chemotherapy significantly decreases serum CD8 + levels in local advanced breast cancer patients.Keyword: CD8 +, locally advanced breast cancer, immune system, neo-adjuvant chemotherapy&#x0D;

Consensus statement on tumour bed localization for radiation after oncoplastic breast surgery.

Oncoplastic surgery (ops) is becoming the new standard of care for breast-conserving surgery, leading to some challenges with adjuvant radiation, particularly when accurate tumour bed (tbd) delineation is needed for focused radiation (that is, accelerated partial breast irradiation or boost radiation). Currently, no guidelines have been published concerning tbd localization for adjuvant targeted radiation after ops. A modified Delphi method was used to establish consensus by a panel of 20 experts in surgical and radiation oncology at the Canadian Locally Advanced Breast Cancer National Consensus Group and in a subsequent online member survey. These are the main recommendations:■ Surgical clips are necessary and should, at a minimum, be placed along the 4 side walls of the cavity, plus 1-4 clips at the posterior margin if necessary.■ Operative reports should include pertinent information to help guide the radiation oncologists.■ Breast surgeons and radiation oncologists should have a basic understanding of ops techniques and work on "speaking a common language."■ Careful consideration is needed when determining the value of targeted radiation, such as boost, in higher-level ops procedures with extensive tissue rearrangement. The panel developed a total of 6 recommendations on tbd delineation for more focused radiation therapy after ops, with more than 80% agreement on each statement. All are summarized, together with the corresponding evidence or expert opinion.

Predictors of Neoadjuvant Chemotherapy Response in Breast Cancer: A Review.

Neoadjuvant chemotherapy (NAC) largely increases operative chances and improves prognosis of the local advanced breast cancer patients. However, no specific means have been invented to predict the therapy responses of patients receiving NAC. Therefore, we focus on the alterations of tumor tissue-related microenvironments such as stromal tumor-infiltrating lymphocytes status, cyclin-dependent kinase expression, non-coding RNA transcription or other small molecular changes, in order to detect potentially predicted biomarkers which reflect the therapeutic efficacy of NAC in different subtypes of breast cancer. Further, possible mechanisms are also discussed to discover feasible treatment targets. Thus, these findings will be helpful to promote the prognosis of breast cancer patients who received NAC and summarized in this review.

P078: Analysis of surgical and oncological outcomes of breast conservation surgery following neo adjuvant chemotherapy in locally advanced breast cancer

Introduction: Neoadjuvant chemotherapy (NACT) is the initial modality of treatment in locally advanced breast cancer (LABC). One of the goals is to reduce the extent of local surgery of breast and axilla. We present our initial experience of NACT followed by Breast Conservation Surgery (BCS) in patients with LABC.

Quality-of-Life and Surgical Outcomes for Breast Cancer Patients Treated with Therapeutic Reduction Mammoplasty Versus Mastectomy with Immediate Reconstruction.

Therapeutic reduction mammoplasty (TRM) is a safe and effective surgical technique that has oncologic outcomes comparable with those achieved by mastectomy. This study aimed to compare surgical and patient-reported outcomes between breast cancer patients treated with TRM and those who had mastectomy with immediate reconstruction (MIR). A 4-year, single-institution, retrospective cohort study analyzed breast cancer patients undergoing TRM and MIR. Patient characteristics and perioperative data were collected from electronic records. Patient-reported outcome data were collected via BREAST-Q questionnaires preoperatively, then 3months and 12months postoperatively. A subgroup analysis was performed on locally advanced breast cancer (LABC) patients for TRM and MIR. The study included 249 breast reconstructions, of which 77 (31%) were TRM and 172 (69%) were MIR. The mean follow-up time was 2.4 ± 1.2years. Compared with MIR, TRM had significantly lower major complication rates (9% vs 21%; p = 0.02) and fewer revisionary surgeries (5% vs 37%; p < 0.0001). At 1year postoperatively, TRM had a significantly greater change in satisfaction with breasts, (+ 27.7 vs + 4.6; p < 0.01) and sexual well-being (+ 20.0 vs - 5.5; p = 0.02) than MIR. For select breast cancer patients, TRM continues to be a safe and effective alternative to mastectomy. The current study demonstrated that TRM patients had fewer major complications and revisionary surgeries, as well as better patient-reported outcomes than MIR.

Correlation between peripheral blood inflammatory indicators and pathologic complete response to neoadjuvant chemotherapy in locally advanced breast cancer patients.

The immune system plays a fundamental role in the response to neoadjuvant chemotherapy (NAC) of locally advanced breast cancer (LABC) patients. Patients with pathological complete response (pCR) after NAC have a higher survival rate. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are peripheral blood indicators of inflammatory response. This investigates the correlation between NLR, PLR, LMR, and other clinicopathological features of breast cancer patients before receiving NAC and pCR.Data of LABC patients who underwent NAC between 2009 and 2018 were retrospectively reviewed. Each patient's peripheral complete blood count was recorded before starting NAC. The cut-off values for neutrophils, lymphocytes, monocytes, and platelets in the peripheral blood and NLR, PLR, and LMR were determined by receiver operating characteristic curve analyses.The records of 131 patients were analyzed and divided into two groups, pCR (+ve) and pCR (-ve), and their clinicopathological features and laboratory findings were compared. pCR was achieved in 23.6% of patients. The cut-off values of neutrophils, lymphocytes, monocytes, and platelets at the time of diagnosis and NLR, PLR, and LMR were, respectively, 4150 μL, 2000 μL, 635 μL, 271 × 10 μL, 1.95, 119, and 3.35. The pCR rate was higher in patients with low neutrophil count, low NLR, and high lymphocyte count (P = .002, <.001, and .040, respectively).As per the findings of multivariate logistic regression analysis, the independent predictive factors of pCR were clinical tumor size T1 and T2, grade 3, ER negativity, and low NLR (P = .015, .001, .020, .022, and .001, respectively).While NLR was found to be an independent predictive factor of pCR in LABC patients receiving NAC, a similar result was not observed for PLR and LMR. NLR can be a useful biomarker for predicting the response of patients receiving NAC.

Locally advanced breast cancer: an observational study for the delay in presentation of patients

Background: Breast cancer is the most common cause of cancer in women and cancer related mortality all over the world. There is strong evidence that delayed diagnosis of breast cancer is associated with poor survival. At our center most of the patients with breast cancer presented as locally advanced breast cancer (LABC) which drew our attention to find out the reasons of delay and its association with different socio-demographic variables.Methods: We enrolled 50 histologically proven cases of LABC in this study. With help of semi structured interview, questions were asked from each patient which could reflect their understanding about the disease to find likely reasons for their delayed presentation, including socioeconomic status.Results: In present study most of our patients were more than 45 years, married. 88% presented late due to unawareness and ignorance about nature and severity of breast cancer disease, 86% had financial issues, 64% had shyness as reason, 20% wasted time by taking alternative treatment, 52% presented late due to painless lump; 30% had fear of losing breast, 18% didn’t get support from family, 4% presented late due to other reasons.Conclusions: Awareness and knowledge of breast cancer was found to be poor amongst sufferers prior to their diagnosis, making it important reason for delayed presentation. Other significant factors being socioeconomic status and education. The need for increased awareness and use of screening practices was identified to be essential for early diagnosis of the disease and for improved outcomes.

Long-term outcomes of preoperative radiotherapy in locally advanced breast cancer: Analysis of Surveillance, Epidemiology, and End Results (SEER) database.

e12600 Background: Currently the treatment paradigm for locally advanced breast cancer (LABC) is multimodality therapy with neoadjuvant systematic treatment, surgery and postoperative radiation therapy (RT). However, with improving outcomes from systematic therapy, the survival rates remain unpromising, which leads to the investigation of the concept of preoperative RT in LABC due to the potential advantages including a possible tumor downstaging and better cosmetic outcomes. We evaluated the overall survival (OS) and breast cancer specific survival (BCSS) of preoperative versus postoperative RT in LABC patients. Methods: Patients diagnosed with non-inflammatory LABC (defined as T3 N1, T4 N0, any N2 or N3, and M0) who received RT before or after surgery between 2010 and 2015 were identified using the SEER database. OS and BCSS were analyzed using Kaplan-Meier method and multivariate Cox proportional hazards model. Results: Among 19249 patients with LABC, 140 (0.7%) received preoperative RT and 19109 (99.3%) received postoperative RT. Overall, 5-year survival and BCSS are 59% and 63% in the preoperative RT group while 77% and 80% in the postoperative RT group. In all patients, treatment with preoperative RT was significantly associated with poor OS (HR 1.82, 95%CI 1.25 to 2.45, P &lt; 0.001) and BCSS (HR 2.00, 95%CI 1.46 to 2.73, P &lt; 0.001) after adjustment for other clinically relevant factors. However, there were no significant difference in terms of both OS and BCSS in ER+ (OS: HR 1.44, 95%CI 0.91 to 2.27, P = 0.12; BCSS: HR 1.55, 95%CI 0.94 to 2.54, P = 0.08) and HER2+ patients (OS: HR 1.33, 95%CI 0.55 to 3.22, P = 0.53; BCSS: HR 1.64, 95%CI 0.67 to 3.97, P = 0.28). Conclusions: Overall, preoperative RT in LABC may reduce overall survival and breast cancer specific survival. However, OS and BCSS were independent of radiation sequence for ER+ and HER2+ patients. This finding warrants further exploration of potential mechanisms of the disparity and the definitive role of preoperative RT in the multimodality therapy of LABC patients.

Neoadjuvant chemotherapy in locally advanced breast cancer: Clinicopathological characteristics and correlation with pathological complete response.

e12658 Background: The data regarding incidence, response rates to neoadjuvant chemotherapy (NACT) and factors affecting pathological complete response (pCR) rate in locally advanced breast cancer (LABC) patients are lacking from India. Methods: This ambispective study was carried out at B.R.A., I.R.C.H, AIIMS, New Delhi, in between period of January 2013 to December 2019. We screened 1500 cases of breast cancer who presented to our institute and found 600 cases to be LABC,425 patients were started on NACT, 284 had undergone surgery and were included in our analysis. Results: The median age of diagnosis was 46 years (range 24-72years). Fifty four percent cases were postmenopausal, 54% had a left sided cancer,45 % right sided cancer,1 % had bilateral breast cancer. The median duration of symptoms was 5 months. The clinical stage according to AJCC staging system was Stage IIB – 11%(32), IIIA -21 % (58), IIIB- 60%(169) and IIIC- 8%(24) .Sixty five percent(186) cases presented with clinical skin involvement and 80% (228) patients has clinical node positivity.In our cohort 52% (148) cases were hormone positive (ER/PR positive), 42 %(119) cases were HER2/neu positive, 30%(84) were triple negative breast cancer (TNBC), 23 % (67) were positive for ER/PR and HER2/neu. Ninety percent of the cases were able to receive the planned neoadjuvant treatment before surgery. Post NACT 83% cases had a modified radical mastectomy (MRM) and 17% were able to undergo breast conserving surgery (BCS).Overall pCR was achieved in 59(21%) cases, 17% in hormone positive cases, 25% in HER2/neu positive cases (30% in cases receiving HER2/neu directed therapy vs 20% in cases who didn’t receive HER2 /neu directed therapy) and 27% in TNBC cases. During the study period 54 cases (19%) had relapsed,8 cases (3%) had a local relapse and a 46 cases (16%) had a systemic relapse. Grade ¾ toxicity occurred in 25 % cases, the most common were diarrhea, neutropenia, CINV, oral mucositis and thrombocytopenia and other rare toxicities (DVT, hand foot syndrome,myalgia). Febrile neutropenia was recorded in 2.5 % cases. There were 2 induction deaths. Stage II, absence of ER/PR expression showed statistically significant correlation with path CR rates. Conclusions: Locally advanced breast cancer constitutes around 40% cases at our institute. Post NACT pCR was achieved in 21% of cases, HER2/neu positive cases and TNBC showed higher pCR rates. The factors affecting pCR rate were absence of ER/PR expression and stage II disease.

Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) for advanced breast cancer patients with high risk for Hereditary Breast and Ovarian Cancer Syndrome (HBOC).

e13549 Background: Local Advanced Breast Cancer (LABC) is associated with high risk of death. NAC is a safe and effective approach for these populations. pCR is a proven prognostic factor in several studies of NAC. HBOC is associated to high risk of breast cancer usually in young age and especially for BRCA1 mutations with a basal phenotype. The aim of this study was to evaluate the influence of BRCA mutational status on frequence of pCR. Methods: this is part of a retrospective, observational study of prevalence of HBOC among patients admitted for cancer therapy in our institution. Since August, 2018 over 300 pte suspected for HBOC (by NCCN criteria) have been screened for NGS with a 31-gene painel. Statistical analysis performed Person X2/Fisher and logistic regression ( p&lt; 0.05; SPSS 20.0). Results: Most pte were women (80%), with median age of 38y (22-72y), most tumors were (80%) stage III, Luminal B (23%) and TNBC (36%). Pathogenic mutations were identified in 34%(n = 28) of the sample ( BRCA1 50%, BRCA2 16.7%, PALB2 16.7%, follow by TP53, PMS2, XRCC2, MUTYH, BARD1 and ATM with 2.8% each).The majority of patients had more than 1 NCCN criteria: age &lt; 45y (83%), family member with BC &lt; 50y (24%) or TNBC (33%) the most common. TNBC tumors had stronger association with germline mutation ( p&lt; 0.001). Regarding response rate there were 13 stable disease (SD), 5 progressive disease (PD), 43 pCR and 39 pathological partial response (pPR). There were no differences in pRC among mutated or no mutated pte, p= 0,170. However, among mutated TNBC there were strong correlation with more pCR, p&lt; 0,006. There was no difference on pCR rate related to mutation status (BRCA vs Non-BRCA), p = 0,84. Conclusions: the present study corroborates other data about the impact of germline mutation status over pCR after NAC for LABC, except for mutated TNBC population, whose seems to be more NAC sensitive.

Preoperative treatment of HER2-positive breast cancer

Preoperative chemotherapy is more and more frequently used in the treatment of localized and locally-advanced breast cancer. This approach not only creates optimal conditions for organ-sparing surgery but also provides us with valuable information on the biology and chemosensitivity of cancer. This data is then crucial for the choice of systemic adjuvant therapy. The availability of two anti-HER2 targeted agents (pertuzumab and trastuzumab) for the neoadjuvant treatment of breast cancer significantly improves the efficacy of this approach. Significantly increased percentage of patients experiencing complete pathological response correlates with improved outcomes. This article is aimed at summarizing current knowledge regarding the role of pertuzumab in neoadjuvant treatment of HER2-positive breast cancer and comprises essential guidelines for the optimal use of currently reimbursed therapies in this disease.

Rhomboid Flap Reconstruction after Mastectomy for Locally Advanced Breast Cancer.

In patients undergoing mastectomy for locally advanced breast cancer (LABC), surgical skin flap reconstruction is sometimes required in order to cover large skin defects. This study assessed the efficacy of local, cutaneous (rhomboid) flap reconstruction after mastectomy by comparing data from patients with LABC requiring local flap reconstruction after mastectomy and those that underwent mastectomy alone. Data from 68 patients with LABC who underwent mastectomy were reviewed retrospectively; 14 underwent local (rhomboid) flap reconstruction after mastectomy (local flap group) and 54 underwent direct closure after mastectomy (direct closure group). A pinch test was performed to determine the closure method. Data on the operation, postoperative complications, and postoperative quality of life (QOL) were compared between groups. It was possible to close defects in the local flap group that were significantly larger than those in the direct closure group (p=0.0002). There was no significant difference in postoperative complications between groups. Although operative duration was significantly longer in the local flap group than in the direct closure group (p=0.016), the average difference was only 25 minutes. There was no significant difference in variables related to postoperative QOL. Rhomboid flap reconstruction was effective for covering large defects after mastectomy in patients with LABC.

Pattern and Predictors of Locoregional Failure in Locally Advanced Breast Cancer Following Neoadjuvant Chemotherapy and Modified Radical Mastectomy with or without Radiotherapy: Retrospective Cohort Analysis of Patients in a Tertiary Hospital Breast Cente

Objective. The study aimed to identify the pattern and clinicopathologic factors associated with locoregional failure (LRF) in locally-advanced breast cancer (LABC) patients who received neoadjuvant chemotherapy (NAC) and modified radical mastectomy (MRM) with or without adjuvant radiotherapy (RT).Methods. Retrospective cohort analysis of LABC patients who developed LRF following NAC and MRM with or without RT in the Breast Care Center, Philippine General Hospital from 2007-2010 was done. Clinicopathologic and treatment factors were compared between patients who developed and did not develop recurrence using Student's t-tests and Chi-square tests and logistic regression analysis, with p values ≤0.05 considered significant.Results. A total of 63 patients were included, 34 with locoregional recurrence (LR) and 29 without. Two-year locoregional recurrence rate (LRR) was 54% with mean time to recurrence at 263 days and chest wall as most common site. Simple logistic regression analysis showed age distribution, pathologic nodal status (pN), percentage positive pathologic lymph nodes, pathologic stage, lymphovascular invasion, and adjuvant RT to be predictors of LR. Furthermore, pN (OR 1.31, CI 1.07-1.59, p=0.01) and adjuvant RT (OR 0.14, CI 0.04-0.53, p=0.004) were independent predictors of LR on multiple logistic regression analysis. In the subset of patients without adjuvant RT, no independent predictor of LR was found on multiple logistic regression analysis.Conclusion. Among patients with LABC who received NAC and MRM, locoregional recurrence occurred frequently, usually in the chest wall and within a year of treatment. The absence of adjuvant radiotherapy and increased number of positive pathologic lymph nodes were predictive of locoregional recurrence.

P10 Clinical and pathologic tumor response following response-guided neoadjuvant chemotherapy for locally advanced breast cancer in the Philippine General Hospital – Breast Care Center

Background and purpose Neoadjuvant chemotherapy is recommended for locally advanced breast cancer (LABC) to improve surgical options and to provide an in-vivo assessment of response to treatment. The Philippine General Hospital (PGH) Breast Care Center has adopted a protocol of response-guided approach to allow for tailoring of the chemotherapy regimen being administered. This study aims to describe the clinical and pathologic tumor response of LABC patients after response-guided neoadjuvant chemotherapy. Methods This is a retrospective cohort of 128 patients with LABC who underwent neoadjuvant chemotherapy at the PGH Breast Care Center using sequential doxorubicin/cyclophosphamide-docetaxel (AC-T) regimen from July 2013 to June 2018. Clinical and pathologic response rates were obtained. Patients were categorized into either good or poor responders and were analyzed according to specific clinicopathologic factors. Results The mean clinical tumor response was at 80% with 14 patients (11%) achieving a pathologic complete response (PCR). The Her2 enriched subtype had the highest PCR rate (23.5%). Interestingly, 2 patients who initially had poor response to AC but had good response upon shifting to T attained PCR. A comparison of the clinicopathologic variables in patients with good or poor response to chemotherapy showed that there are significantly more patients with good response to the AC regimen if the patient is pre-menopausal (p=0.04), those with ductal histology (p=0.03), those with a triple negative subtype (p=0.002) and those with HR+HER2+ subtype (p=0.03). Intrinsic subtype did not appear to be a significant factor for a better response in those who received Docetaxel. A Spearman’s Rho score of 0.69 (p-value <0.0001) indicates a strong association between the pathologic and clinical responses. Conclusion Neoadjuvant chemotherapy allows direct and early evaluation of treatment response. This promotes personalized treatment and may justify early shifting to another chemotherapy regimen for non-responders as in response-guided neoadjuvant chemotherapy. 1. von Minckwitz, et. al. Response-Guided Neoadjuvant Chemotherapy for Breast Cancer. J Clin Oncol 31:3623-3630. DOI: 10.1200/JCO.2012.45.09402. Kim S.I, et. al. Molecular subtypes and Tumor Response to Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer. Oncology 2010;79:324-330. http://doi.org/10.1159/000322192

Surgical and Oncologic Outcomes of Nipple-Sparing Mastectomy for a Cohort of Breast Cancer Patients, Including Cases with High-Risk Features

BackgroundNipple-sparing mastectomy (NSM) remains controversial in patients with high-risk breast cancer. The objective of this study was to assess surgical and oncologic outcomes of NSM and to evaluate associations of outcomes with high-risk features. MethodsA retrospective review was conducted of all NSM cases performed for breast cancer at 2 academic cancer centers between January 2013 and August 2018. ResultsOf the 175 patients who underwent NSM, 13 (7.4%) had locally advanced breast cancer (LABC), 52 (29.2%) had previous neoadjuvant chemotherapy, 21 (12.0%) had previous radiation therapy, 40 (22.8%) received postmastectomy radiation, 27 (15.4%) had de-epithelialized skin reduction, and 13 (7.4%) had free nipple grafting. The median duration of follow-up was 24 months. Nipple necrosis (4 cases; 2.2%) was associated with previous radiation (9.5%; P = .018), skin reduction (11.1%; P = .001), and nipple grafting (15.4%; P = .001). The nipple–areolar complex margin (NAC) was involved with invasive disease in 1 case. Local recurrence occurred in 8 cases (4.6%), with 1 in-NAC recurrence. Overall survival was 98.3%, and disease-free survival (DFS) was 88.6%. LABC was associated with worse DFS (hazard ratio, 4.28; P = .011), with all 4 recurrences being distant. ConclusionsPrevious radiation, skin reduction, and nipple grafting are associated with an increased risk of NAC necrosis. None of these should be considered absolute contraindications, but patients should be counseled appropriately. Although LABC is associated with worse DFS, relapses are systemic. Longer follow-up is needed to establish oncologic safety in unselected breast cancer patients.

Prognostic Significance of Molecular Profile in Non-metastatic Invasive Breast Cancer: A Multicentre Study from India

To give the molecular profiling and its association with DFS among women with early breast cancer (EBC) and locally advanced breast cancer (LABC). This cohort study used secondary data from six tertiary cancer hospitals in south India. DFS was calculated from the date of treatment completion to local or distant relapse, death, or last follow-up or date of censoring (31 December 2018) whichever was earlier. Adjusted hazard ratios (HRs) and 95% CIs were calculated using Cox regression analysis. Of 837 women, 288 (34.4%) had EBC and 549 (65.6%) had LABC. The mean age was 52.1 years (SD 10.4). Luminal A was the most frequent molecular subtype (36.7%) followed by triple-negative (25.4%), Her2/neu-enriched (14.9%) and luminal B Her2/neu-positive subtypes (13.1%). Three-year DFS was 92% among EBC and 76% among LABC. Among EBC group, molecular profile was not associated with DFS. On adjusted analysis among LABC group, when compared to luminal A, triple-negative [aHR 3.95 (95% CI 1.78, 7.88)] and Her2-enriched [aHR 2.6 (95% CI 1.21, 5.61)] were associated with relapse. Certain molecular subtypes predicted survival in LABC group. However, early diagnosis and treatment appear to nullify this effect on survival.

Study of targeted four node sampling of axilla in management of carcinoma of breast

Background: Axillary lymph node sampling is considered as one of the most pivotal investigations in determining the lymph node status in management of carcinoma breast. The present study attempts to assess sensitivity, specificity and positive predictive value of axillary four node sampling (FNS) in management of carcinoma of breast, and its efficacy in downstaged patients.Methods: A total of 35 patients, node negative operable cases of carcinoma breast and locally advanced breast cancer (LABC) patients downstaged after 3 cycles of neoadjuvant chemotherapy, were enrolled. Lymph node mapping was done by injecting 3 - 5 ml of methylene blue dye, just before surgery. Level 1 lymph nodes stained by methylene blue were sampled and axillary dissection was carried out, level 3 lymph nodes were identified and sampled, rest of the axillary dissection specimen was sent as a separate sample for histopathological examination , node positivity was compared in level 1 and level 3 , and conclusions were drawn.Results: The sensitivity, specificity for FNS in node negative operable cases were found to be 83.33% and 91.3% respectively. The negative and positive predictive value were found to be 95.40% and 71.42% respectively. Specificity of FNS in LABC downstaged patients was found to be 40%.Conclusions: Targeted four node sampling using methylene blue dye can be considered as an alternative method for sentinel lymph node. Further study should be conducted to establish it as a reliable method for axillary lymph node staging.