Breast-conserving Surgery Eligibility Research Articles

Abstract PO2-02-10: Predicting the feasibility of breast conserving surgery using pre-treatment standard of care DCE-MRI: a novel clinical decision support tool for breast cancer surgical planning

Abstract Background: The decision-making process regarding breast cancer treatment options, specifically breast conserving surgery (BCS) versus mastectomy, is a complex and sensitive matter that takes into account the patient's preferences and their eligibility for BCS. A range of anatomical factors, such as tumor size, breast size, and proximity of the tumor to the skin, can influence the surgeon's recommendation regarding BCS or mastectomy. While mastectomy may be the only viable option for patients with large tumors, those with smaller tumors often have the opportunity to collaboratively decide with their surgeon on the most appropriate approach to ensure oncologic success and minimize potential cosmetic deformity. To facilitate this decision-making process, we developed a tool capable of providing informed recommendations on BCS or mastectomy based on standard of care imaging patient data. By integrating these recommendation capabilities, we aim to enhance the decision-making process and improve patient outcomes in breast cancer treatment. Methods: To assist surgeons and patients in determining a patient’s eligibility for breast conserving surgery (BCS), we developed the BCS Feasibility Score. The BCS Feasibility Score is generated from a binary classifier machine learning model and is representative of the probability that a given patient could receive BCS. The score is based solely on the output from TumorSight Viz, a software platform that uses only pre-treatment T1-weighted DCE MRI and applies a suite of deep learning algorithms to segment the patient’s disease and the surrounding breast tissues. From the multi-tissue segmentation generated using TumorSight Viz, we extracted 25 spatial morphology features to use in the model development process. The training and testing sets were a subsample of a publicly available dataset (Saha, et al, 2018). We selected patients that received either BCS or mastectomy and had a viable T1-weighted DCE MRI. Bi-lateral cases were excluded. The total training/testing set consisted of n = 749 cases, 363 of which received mastectomy and 386 who received BCS. Before model training occurred, we split 20% of the sample to use as the test set. We then trained a random forest classifier across a range of pre-set hyper-parameters, using a total of 25 features as inputs, and using 5x cross-validation in the training set. We then assessed model performance in the testing set only. Results: In the test set, 76 cases received BCS versus 74 that received mastectomy. We successfully predicted BCS in 56 out of 76 cases (74%), and mastectomy in 46 out of 74 cases (62%). Overall, we observed an AUC = 0.76 and an F1 score = 0.66, indicating moderate to strong model performance. The most important features in the model, as measured by SHAP values, included the axis aligned tumor longest dimension (mm), the closest distance between the tumor and the nipple (mm), the volume of the tumor convex hull (mL; dilated uni-centrically), and the ratio of tumor convex hull volume to breast volume. We tested the model’s performance in a fully independent holdout validation set of 579 cases. Within this validation set, 335 patients received BCS versus 244 received mastectomy. We successfully predicted BCS in 254 out of 335 cases (76%), and mastectomy in 149 out of 244 cases (61%). Overall, we observed an AUC = 0.75 and an F1 score = 0.63. Validation set performance mirrored results observed in the test set, indicating strong generalizability. In the validation set, comparing patients who underwent BCS to those who underwent mastectomy, we observed significant differences across all four of the most predictive features. Conclusion: TumorSight Viz and the BCS Feasibility Score help empower both patients and clinicians with information and tools to facilitate surgical planning decisions. Citation Format: John Pfeiffer, Bradley Feiger, Anuja Antony, Joseph Peterson. Predicting the feasibility of breast conserving surgery using pre-treatment standard of care DCE-MRI: a novel clinical decision support tool for breast cancer surgical planning [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-02-10.

Neoadjuvant chemotherapy for stage II–III breast cancer: a single-center experience

IntroductionWe conducted this study to reflect a single-center experience with the use of neoadjuvant systemic chemotherapy (NAC) for the management of women with operable breast cancer.MethodsWe conducted a retrospective chart review on all women presenting with operable, stage II–III, breast cancer and were scheduled for NAC at Suez Canal University Hospital. The primary outcome of this study was to estimate the proportion of patients with breast cancer who become eligible for breast-conserving surgery (BCS) after (NAC).ResultsA total of 147 patients were included. Before the initiation of chemotherapy, only 66 (44.9%) patients were indicated for (BCS). A total of 40 (49.4%) new patients, out of the 81 patients who were ineligible before chemotherapy, became eligible for BCS after NAC (95% CI 39.3–61.9%). On the other hand, 8 (12.1%) patients became ineligible for BCS after NAC, out of 66 patients who were initially eligible. Out of the 98 eligible patients for BCS after chemotherapy, 72 (73.5%) patients underwent the surgery, and the remaining 26 (26.5%) patients chose modified radical mastectomy (MRM). A total of 55 out of 72 (76.4%) patients achieved pathological complete response (pCR). One woman (0.1%) experienced relapse in the 3rd year of follow-up and three women (2%) experienced relapse in the 5th year of follow-up. We found a statistically significant relationship between patients who became eligible for breast-conserving surgery and both age and estrogen receptor negativity (p = 0.001 and 0.007, respectively).ConclusionNAC can play a crucial role in increasing the rate of eligibility for BCS among women with operable, stage II–III, breast cancer.

Long-Term Patient-Reported Outcomes Comparing Oncoplastic Breast Surgery and Conventional Breast-Conserving Surgery: A Propensity Score-Matched Analysis.

Oncoplastic breast surgery (OBS) combines plastic surgery techniques with conventional breast-conserving surgery (BCS) and expands BCS eligibility. Limited data are available on patient-reported outcomes (PROs) after OBS. Here we compare long-term PROs after OBS and BCS utilizing the BREAST-Q. Women undergoing OBS or BCS between 2006 and 2019 who completed ≥ 1 long-term BREAST-Q survey 3-5 years postoperatively were identified. Baseline characteristics were compared between women who underwent OBS/BCS. Women who underwent OBS were paired with those who underwent BCS using 1:2 propensity matching [by age, body mass index (BMI), race, T stage, and multifocality]. BREAST-Q scores were compared preoperatively and 3-5 years postoperatively. A total of 297 patients were included for analysis (99 OBS/198 BCS). Women who underwent OBS were younger (p < 0.001) and had higher BMI (p = 0.005) and multifocal disease incidence (p = 0.004). There was no difference between groups in nodal stage, re-excision rates, axillary surgery, chemotherapy, endocrine therapy, or radiotherapy. After propensity matching preoperatively, women who underwent OBS reported lower psychosocial well-being (63 versus 100, p = 0.039) but similar breast satisfaction and sexual well-being compared with women who underwent BCS; however, only three patients who underwent BCS had preoperative BREAST-Q scores available for review. In long-term follow-up, women who underwent OBS reported lower psychosocial scores (74 versus 93, p = 0.011) 4 years postoperatively, but not at 5 years (76 versus 77, p = 0.83). There was no difference in long-term breast satisfaction or sexual well-being. Women who undergo OBS present with a larger disease burden and may represent a group of non-traditional BCS candidates; they reported similar long-term breast satisfaction and sexual well-being compared with women who undergo BCS. While women who underwent OBS reported lower psychosocial well-being scores preoperatively and during a portion of the follow-up period, this difference was no longer seen at 5 years postoperatively.

A prospective cohort study identifying radiologic and tumor related factors of importance for breast conserving surgery after neoadjuvant chemotherapy

IntroductionNeoadjuvant chemotherapy (NAC) is an established treatment option for early breast cancer, potentially downstaging the tumor and increasing the eligibility for breast-conserving surgery (BCS). The primary aim of this study was to assess the rate of BCS after NAC, and the secondary aim was to identify predictors of application of BCS after NAC. Materials and methodsThis was an observational prospective cohort study of 226 patients in the SCAN-B (Clinical Trials NCT02306096) neoadjuvant cohort during 2014–2019. Eligibility for BCS was assessed at baseline and after NAC. Uni- and multivariable logistic regression analyses were performed using covariates with clinical relevance and/or those associated with outcome (BCS versus mastectomy), including tumor subtype, by gene expression analysis. ResultsThe overall BCS rate was 52%, and this rate increased during the study period (from 37% to 52%). Pathological complete response was achieved in 69 patients (30%). Predictors for BCS were smaller tumor size on mammography, visibility on ultrasound, histological subtype other than lobular, benign axillary status, and a diagnosis of triple-negative or HER2-positive subtype, with a similar trend for gene expression subtypes. Mammographic density was negatively related to BCS in a dose-response pattern. In the multivariable logistic regression model, tumor stage at diagnosis and mammographic density showed the strongest association with BCS. ConclusionThe rate of BCS after NAC increased during the study period to 52%. With modern treatment options for NAC the potential for tumor response and BCS eligibility might further increase.

Abstract P1-09-06: Save the breast after neoadjuvant therapy – identifying radiological and tumor related factors of importance for breast conserving surgery after neoadjuvant chemotherapy

Abstract Background: Neoadjuvant chemotherapy (NAC) is an established treatment option in early breast cancer. NAC potentially downstages the tumor and, combined with oncoplastic techniques, may increase the eligibility for breast conserving surgery (BCS). NAC can also result in less surgical morbidity of the axilla if axillary clearance can be avoided. In addition, preoperative medical treatment allows for a thorough evaluation of treatment response and lays the foundation for adjuvant treatment decisions. The aim of the study was to prospectively estimate the proportion of BCS post NAC and the relation to well-defined factors associated with BCS post NAC. Materials and methods: This observational prospective cohort study included 226 patients in the SCAN-B neoadjuvant cohort (Clinical trials: NCT02306096) receiving NAC between 2014 and 2019. Eligibility for BCS was based on the assessment of the surgeon at time of diagnosis and again post NAC. All the covariables were defined at time of diagnosis from mammograms and core needle biopsies, except for pathological complete response (pCR). Treatment generally consisted of 6 to 7 three-weekly treatment cycles of anthracycline- and taxane-based chemotherapy, given in sequence. In HER2-positive disease, HER2-directed antibodies were added as appropriate.The primary aim was to estimate the proportion of BCS after NAC and the secondary aim was to evaluate factors as predictors of BCS, including gene expression and surrogate molecular subtypes (St. Gallen), breast density, and other putative modifying factors.Uni- and multivariable logistic regression analysis were performed including covariates of clinical relevance and/or associated with the outcome measures (BCS versus mastectomy). Results: The BCS rate increased during the study years, from 37% to 52%. pCR was achieved in 69 patients (30%). Predictors with a negative association to BCS were larger tumor size on mammography (T3 vs T1) (odds ratio (OR)=0.20, 95% confidence interval (CI) [0.06,0.64]), lack of visibility on ultrasound (OR=0.08, 95% CI [0.001,0.63]), lobular histological subtype vs other subtypes (OR=0,20, 95% CI [0.06,0.61)). Factors positively associated with BCS were benign axillary lymph node status (OR=2.26, 95% CI [1.26,4.06]) and surrogate molecular subtypes; patients with triple negative and HER-2 positive tumors had the highest probability of receiving BCS, 65% and 54%, respectively. Gene expression subtypes had a similar trend of being associated with BCS; patients with basal like and HER-2 enriched tumors had higher odds ratio for BCT than patients with luminal subtypes (Table 1). In the multivariable logistic regression analysis, tumor size on mammography and axillary status had the strongest association to BCS (OR=0.95, 95% CI [0.92,0.98] and OR=2.08, 95% CI [0.99,4.35], respectively). Conclusions: Our study shows that the rate of BCS after NAC increased over the study years, but mastectomy rate in the study was still close to 50%. With increasing number of patients achieving pCR after NAC, the BCS rate should be possible to increase further. Predictors of BCS after NAC were identified, and benign axillary lymph nodes and smaller tumor size defined at time of diagnosis were the strongest predictors of BCS, supporting that initial tumor stage was important for the choice of surgery after NAC. Table 1. Baseline characteristics and univariable logistic regression. 1. Determined by biopsy or sentinel node. 2. Only tumors visible on mammography. 3. Defined as ypT0/ypTis/ypN0. Citation Format: Kim Gulis, Julia Ellbrant, Pär-Ola Bendahl, Tor Svensjö, Johan Vallon-Christersson, Ida Dalene Skarping, Niklas Loman, Lisa Rydén. Save the breast after neoadjuvant therapy – identifying radiological and tumor related factors of importance for breast conserving surgery after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-09-06.

The Effect of Age on Outcomes After Neoadjuvant Chemotherapy for Breast Cancer.

Younger women (age ≤40years) 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 ≥61years. 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. 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 41-60years and 29% among those aged ≥61years; 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 ≤40years of age avoided axillary lymph node dissection (ALND) with NAC, versus 39% and 37% in the older groups (p<0.001). 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.

Abstract P2-12-24: Exosomal metabolic signatures are associated with differential response to neoadjuvant chemotherapy in patients with breast cancer

Abstract Background: Neoadjuvant chemotherapy (NAC) is becoming the standard of care for aggressive breast cancer (BC). In patients with BC, NAC can increase eligibility for breast-conserving surgery, lower the excision volume, and assist in evaluating the disease course. NAC may shrink (residual disease, RD) or even eliminate (pathologic complete response, pCR) the tumor. Patients with RD often have a poor long-term prognosis. In contrast, pCR is associated with better long-term survival outcomes. Approximately 30% of patients with BC show pCR after NAC, while the rest exhibit RD. A critical barrier to improving NAC outcomes in patients with BC is the lack of precise molecular targets and limited understanding of the molecular mechanisms underlying differential treatment outcomes in patients with BC receiving NAC. Thus, there is an urgent clinical need to elucidate the underlying molecular regulation associated with NAC resistance. Studies have shown that cellular stress induces the release of small extracellular vesicles known as exosomes, contributing to drug resistance. In this study, we evaluated the ability of exosomal metabolic profiles to predict NAC response in BC patients. Methods: We collected blood samples of 16 patients with BC who received NAC at Grady Memorial Hospitals, USA. Further, total exosomes were isolated from plasma by an ultracentrifugation method and characterized for their concentration (number/ml), size distribution, and exosomal content. Exosome sizes were validated using nanoparticle tracking analysis. RNA, proteins, and metabolites were isolated from exosomes to perform deep multiplatform analyses (viz. miRNA seq, proteomics, and metabolomics) of exosomal cargo to identify various potential biological determinants of NAC response and evaluate their contributions to the risk of RD in patients with BC after NAC. KEGG and HMDB IDs were used for metabolomics data analyses. Various analyses viz. enriched metabolomic pathway analysis, MS peak to pathway analysis (using GSEA and Mummichog), and network explorer analysis were performed using Metaboanalyst online portal to reveal the metabolic signatures in exosomes of BC patients who exhibited pCR and RD after NAC treatment. Results: Among the 16 patients with BC who received NAC, eight patients attained pCR, and eight had RD. Interestingly, we found that patients with pCR secreted 61% fewer exosomes but had 24% larger-sized exosomes than patients with RD following NAC. Furthermore, significant differences in the loading of exosomal cargo were observed between the two groups. Based on these results, we proposed that the differential RNA, protein, and metabolite profile of exosomes might contribute to the higher drug sensitivity in patients with pCR. Our proteomics and miRNA-seq analyses of exosomes from patients with pCR and RD after NAC did not show any significant differences between the groups. However, metabolite set enrichment analysis using MetaboAnalyst revealed that compared to exosomes from patients with pCR, patients with RD were significantly enriched in various metabolic pathways. These pathways included valine, leucine, and isoleucine biosynthesis; phenylalanine metabolism; one-carbon pool folate; and inositol phosphate metabolism. Additionally, MS peak to pathway analysis revealed differential enrichment of various other metabolic pathways, particularly in patients with RD.Conclusions: These data strongly suggest that exosomal metabolic signatures are associated with differential NAC outcomes in patients with BC. We believe that in-depth studies of these metabolite signatures will give essential clues about differential NAC response in patients with BC. Citation Format: Shriya Joshi, Chakravarthy Garalapati, Shristi Bhattarai, Darshan Shimoga Chandrashekar, Sooryanarayana Varambally, Gagan Deep, Ritu Aneja. Exosomal metabolic signatures are associated with differential response to neoadjuvant chemotherapy in patients with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-24.

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

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). 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. 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). 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.

Surgical Treatment After Neoadjuvant Systemic Therapy in Young Women With Breast Cancer

We aimed to investigate eligibility for breast conserving surgery (BCS) pre- and post-neoadjuvant systemic therapy (NST), and trends in the surgical treatment of young breast cancer patients. Young women with breast cancer are more likely to present with larger tumors and aggressive phenotypes, and may benefit from NST. Little is known about how response to NST influences surgical decisions in young women. The Young Women's Breast Cancer Study, a multicenter prospective cohort of women diagnosed with breast cancer at age ≤40, enrolled 1302 patients from 2006 to 2016. Disease characteristics, surgical recommendations, and reasons for choosing mastectomy among BCS-eligible patients were obtained through the medical record. Trends in use of NST, rate of clinical and pathologic complete response, and surgery were also assessed. Of 1117 women with unilateral stage I-III breast cancer, 315 (28%) received NST. Pre-NST, 26% were BCS eligible, 17% were borderline eligible, and 55% were ineligible. After NST, BCS eligibility increased from 26% to 42% (P < 0.0001). Among BCS-eligible patients after NST (n = 133), 41% chose mastectomy with reasons being patient preference (53%), BRCA or TP53 mutation (35%), and family history (5%). From 2006 to 2016, the rates of NST (P = 0.0012), clinical complete response (P < 0.0001), and bilateral mastectomy (P < 0.0001) increased, but the rate of BCS did not increase (P = 0.34). While the proportion of young women eligible for BCS increased after NST, many patients chose mastectomy, suggesting that surgical decisions are often driven by factors beyond extent of disease and treatment response.

How Often Does Modern Neoadjuvant Chemotherapy Downstage Patients to Breast-Conserving Surgery?

Neoadjuvant chemotherapy (NAC) has been proven to increase breast-conserving surgery (BCS) rates, but data are limited on conversion rates from BCS-ineligible (BCSi) to BCS-eligible (BCSe), specifically, in patients with large tumors. Consecutive patients with stage I-III breast cancer treated with NAC from November 2013 to March 2019 were identified. BCS eligibility before and after NAC was prospectively determined. Patients deemed BCSi before NAC due to large tumor size were studied. Statistical analyses were conducted using Student's t-test, Wilcoxon rank sum test, Chi-square test, Fisher's test, and logistic regression. In this study, 600 of 1353 cancers were BCSi with large tumors; 69% were non-BCS candidates, 31% were borderline-BCS (bBCS) candidates. Of non-BCS candidates, 69% became BCSe after NAC; 66% chose BCS, and 90% were successful. Among bBCS candidates, 87% were BCSe after NAC, 73% chose BCS, and 96% were successful. On univariate analysis, bBCS candidacy, lower cT stage, cN0 status, absence of calcifications, human epidermal growth factor receptor 2 positive (HER2+)/triple negative (TN) receptor status, poor differentiation, ductal histology, and breast pCR were associated with conversion to BCS eligibility. On multivariable analysis, receptor status (hormone receptor positive [HR+]/HER2- ref; odds ratio [OR] HER2+ 1.63, P = 0.047; HR-/HER2- OR, 2.26, P = 0.003) and breast pCR (OR 2.62, P < 0.001) predicted successful downstaging, while larger clinical tumor size (OR 0.86, P = 0.003), non-BCS candidacy (OR 0.46, P = 0.003), cN+ status (OR 0.54, P = 0.008), and calcifications (OR 0.56, P = 0.007) predicted lower downstaging rates. In patients with large tumors precluding BCS, conversion to BCS eligibility was high with NAC, particularly in bBCS candidates. HER2+/TN receptor status predicted successful downstaging, while lower downstaging rates were observed with larger tumors, cN+ status, and calcifications. These factors should be considered when selecting patients for NAC.

Early assessment with magnetic resonance imaging for prediction of pathologic response to neoadjuvant chemotherapy in triple-negative breast cancer: Results from the phase III BrighTNess trial

IntroductionThe ability of breast magnetic resonance imaging (MRI) to predict pathologic complete response (pCR) to neoadjuvant systemic therapy (NST) varies across biological subtypes. We sought to determine how well breast MRI findings following initial treatment on the phase III BrighTNess trial correlated with pCR in patients with triple negative breast cancer (TNBC). MethodsBaseline and mid-treatment imaging and pathologic response data were available in 519 patients with stage II-III TNBC who underwent NST as per protocol. MRI complete response (mCR) was defined as disappearance of all target lesion(s) and MRI partial response (mPR) as a ≥50% reduction in the largest tumor diameter. ResultsOverall, mCR was demonstrated in 116 patients (22%), whereas 166 (32%) had mPR and 237 (46%) had stable/progressive disease (SD/PD). The positive predictive value (PPV), negative predictive value, and overall accuracy of the mid-treatment MRI for pCR were 78%, 56%, and 61%, respectively; accuracy did not differ significantly between gBRCA mutation carriers and non-carriers (52% vs. 63%, p = 0.10). When compared to patients with SD/PD, those with mPR or mCR were 3.35-fold (95% CI 2.07–5.41) more likely to have pCR at surgery. MRI response during NST was significantly associated with eligibility for breast-conserving surgery following completion of treatment (93.1% for mCR vs. 81.6% for SD/PD, p < 0.001). ConclusionsComplete response on mid-treatment MRI in the BrighTNess trial had a PPV of 78% for demonstration of pCR after completion of NST in TNBC. However, a substantial proportion of patients with mPR or SD/PD also achieved a pCR. Clinical trial registrationNCT02032277.

Impact of neoadjuvant chemotherapy and pathological complete response on eligibility for breast-conserving surgery in patients with early breast cancer: A meta-analysis

PurposeWe conducted a meta-analysis of randomised trials evaluating pathological complete response (pCR) and surgical outcomes after neoadjuvant systemic therapy (NST) in patients with early breast cancer (EBC). Patients and methodsThe primary outcome was breast-conserving surgery (BCT) rate. Secondary outcomes were pCR rate and association to BCT. Meta-analyses were performed using random effects models that use inverse-variance weighting for each treatment arm based on evaluable patients. Point estimates are reported with 95% confidence interval (CI), and p < 0.05 was considered statistically significant. ResultsThirty-six studies were identified (N = 12,311 patients). We selected for the analysis 16 of 36 studies reporting both pCR and BCT for at least one treatment arm. Arms per study ranged from one to six; 42 independent units were available to evaluate the association between pCR and BCT. BCT rate ranged 5–76% across arms with an average BCT of 57% (95% CI 52–62%). Significant heterogeneity was observed among the trials (Cochrane Q = 787, p < 0.001, I2 = 97%). In the meta-regression model, BCT rates were not significantly associated with year of first patient-in (p = 0.89), grade (p = 0.93) and hormone-receptor status (p = 0.39). Clinical N-stage (p = 0.01) and human epidermal growth factor receptor (HER2) status (p = 0.03) were significantly associated with BCT. pCR rate ranged 3–60% across studies. The average pCR across all study arms was 24% (95% CI 19–29%). No association was observed between pCR rate in a study arm and the resulting BCT rate in a univariate model (p = 0.34) nor after adjusting for HER2 and clinical nodal status (p = 0.82). In the subset of 14 multi-arm studies, no significant association was seen between the differences in pCR and BCT between treatment arms (p = 0.27). ConclusionspCR does not increase BCT in patients receiving NST for EBC.

Impact of Neoadjuvant Chemotherapy in Stage II–III Triple Negative Breast Cancer on Eligibility for Breast-conserving Surgery and Breast Conservation Rates: Surgical Results From CALGB 40603 (Alliance)

Impact of Neoadjuvant Chemotherapy in Stage II–III Triple Negative Breast Cancer on Eligibility for Breast-conserving Surgery and Breast Conservation Rates: Surgical Results From CALGB 40603 (Alliance)

Neoadjuvant letrozole in postmenopausal estrogen and/or progesterone receptor positive breast cancer: A phase IIb/III trial to investigate optimal duration of preoperative endocrine therapy

BackgroundIn recent years, preoperative volume reduction of locally advanced breast cancers, resulting in higher rates of breast-conserving surgery (BCS), has become increasingly important also in postmenopausal women. Clinical interest has come to center on the third-generation nonsteroidal aromatase inhibitors (AIs), including letrozole, for such neoadjuvant endocrine treatment. This usually lasts 3–4 months and has been extended to up to 12 months, but optimal treatment duration has not been fully established.MethodsThis study was designed as a multicenter, open-label, single-arm, exploratory phase IIb/III clinical trial of letrozole 2.5 mg, one tablet daily, for 4–8 months. The primary objective was to investigate the effect of neoadjuvant treatment duration on tumor regression and BCS eligibility to identify optimal treatment duration. Tumor regression (by clinical examination, mammography, and ultrasound), shift towards BCS eligibility, and safety assessments were the main outcome measures. Standard parametric and nonparametric descriptive statistics were performed.ResultsLetrozole treatment was received by 32 of the enrolled 33 postmenopausal women (median (range): 67.0 (56–85) years) with unilateral, initially BCS-ineligible primary breast cancer (clinical stage ≥ T2, N0, M0). Letrozole treatment duration in the modified intent-to-treat (ITT; required 4 months' letrozole treatment) analysis population (29 patients) was 4 months in 14 patients and > 4 months in 15 patients. The respective per-protocol (PP) subgroup sizes were 14 and 11. The majority of partial or complete responses were observed at 4 months, though some beneficial responses occurred during prolonged letrozole treatment. Compared with baseline, median tumor size in the ITT population was reduced by 62.5% at Month 4 and by 70.0% at final study visit (Individual End). Similarly, in the PP population, respective reductions were 64.0% and 67.0%. Whereas initially all patients were mastectomy candidates, letrozole treatment enabled BCS (lumpectomy) in 22 ITT (75.9%) and 18 PP (72.0%) patients.ConclusionOver half of patients become BCS-eligible within 4 months of preoperative letrozole treatment. While prolonged treatment for up to 8 months can result in further tumor volume reduction in some patients, there is no clear optimum for treatment duration. Letrozole has a favorable overall safety and tolerability profile.Trial registrationClinicalTrials.gov identifier NCT00535418.