Operable Invasive Breast Cancer Research Articles

Interpectoral nodal dissection for invasive breast cancer: A retrospective single institution study from India.

e12585 Background: Interpectoral lymph nodes are one of the axillary lymphatic drainage sites in breast carcinoma. Usually dissection of Interpectoral nodes (IPN) avoided during axillary dissection as they are not the primary lymphatic drainage site. Our study aims to identify the rate of positivity of Interpectoral nodes in invasive breast cancer, predictors of IPN positivity in relation to tumour location, size, grade and hormone receptor status and to evaluate the need for IPN clearance during axillary dissection. Methods: A retrospective analysis of histopathology reports of 367 patients who underwent Axillary dissection in a single centre from Jan 2017-Dec 2022 for breast cancer was analysed. Inclusion criteria: Female Patients with operable Invasive Breast cancer with node positive axilla who underwent axillary dissection (upfront and post chemotherapy). Exclusion criteria: metastatic breast cancer, node-negative patients/sentinel lymph node biopsy, inadequate nodal dissection, and incomplete clinicopathological information. Data was analysed looking for presence of nodes in interpectoral tissue in Axillary dissection and to identify the positivity of interpectoral lymph nodes in specimens. Results: Interpectoral nodal dissection was done in n=216 of the 367 patients. The clinicopathological characters are described in Table. IPN were identified in 35% (n=77) of the 216 Axillary dissection specimens. IPN were positive in 7.8% (17 of 216) of patients who had interpectoral nodal dissection. 22% of the interpectoral lymph nodes removed were positive. As regards tumour size, Rotter's nodes were identified commonly in T3 and T4 tumours and positive in people with N2 and N3 disease. By multivariate analysis, T stage and N stage were the most important determinants of IPN yield and positivity. Site of tumour, neoadjuvant therapy, molecular subtype or Ki 67 were not found to be associated with either presence or positivity of interpectoral nodes. In 5 cases IPN positivity upstaged the nodal stage and in 1 patient it was the only positive node. Conclusions: As IPN is positive in most LABC, whenever axillary dissection is done in such cases Interpectoral nodes can be safely removed while dissecting level III nodes. Nodal recurrence is the most common site of recurrence post mastectomy and hence Interpectoral nodes need to be routinely removed in patients undergoing Axillary dissection for operable breast cancer to enable accurate staging and to prevent local or systemic failure. [Table: see text]

Diagnostic accuracy of pre-operative breast magnetic resonance imaging (MRI) in predicting axillary lymph node metastasis: variations in intrinsic subtypes, and strategy to improve negative predictive value—an analysis of 2473 invasive breast cancer patients

BackgroundThe value and utility of axillary lymph node (ALN) evaluation with MRI in breast cancer were not clear for various intrinsic subtypes. The aim of the current study is to test the potential of combining breast MRI and clinicopathologic factors to identify low-risk groups of ALN metastasis and improve diagnostic performance.Material and methodsPatients with primary operable invasive breast cancer with pre-operative breast MRI and post-operative pathologic reports were retrospectively collected from January 2009 to December 2021 in a single institute. The concordance of MRI and pathology of ALN status were determined, and also analyzed in different intrinsic subtypes. A stepwise strategy was designed to improve MRI-negative predictive value (NPV) on ALN metastasis.Results2473 patients were enrolled. The diagnostic performance of MRI in detecting metastatic ALN was significantly different between intrinsic subtypes (p = 0.007). Multivariate analysis identified tumor size and histologic type as independent predictive factors of ALN metastases. Patients with HER-2 (MRI tumor size ≤ 2 cm), or TNBC (MRI tumor size ≤ 2 cm) were found to have MRI–ALN-NPV higher than 90%, and these false cases were limited to low axillary tumor burden.ConclusionThe diagnostic performance of MRI to predict ALN metastasis varied according to the intrinsic subtype. Combined pre-operative clinicopathologic factors and intrinsic subtypes may increase ALN MRI NPV, and further identify some groups of patients with low risks of ALN metastasis, high NPV, and low burdens of axillary disease even in false-negative cases.

Abstract P6-05-12: Understanding Patient Perspectives on Window of Opportunity Clinical Trial Participation in Breast Cancer

Abstract Background: Window of opportunity (WOO) clinical trials take advantage of the waiting period between a patient’s cancer diagnosis and standard treatment (usually surgery) to evaluate novel cancer therapies and their biologic effects in vivo. These types of trials are being increasingly harnessed in the clinical setting for the safe and rapid evaluation of novel therapeutic strategies in treatment naive patients, thereby expediting drug development. Distinct from neoadjuvant trials, no therapeutic benefit is envisaged and the patient’s standard treatments are not intentionally delayed. The purpose of this study was to understand the patient motivations and perspectives for participating in WOO trials. Methods: This study was conducted at an academic cancer center where two breast cancer WOO trials were ongoing (NCT04781725 and NCT04676516). Eligible patients with newly diagnosed operable invasive breast cancers participating in either of these WOO trials were recruited to this separate study. Patients were provided with a questionnaire that surveyed their motivation and perspectives for participation or lack of participation in the WOO trial Results: From April 2021- May 2022, the study recruited 89 patients with age ranging from of 40-78 yrs with tumors ranging from 1.5-4.3 cm. Surgical wait times ranged from 2-8 weeks. Of the 83 patients that participated in a WOO trial, the most common reasons for participation included (a) the potential to benefit other patients in the future (90%) (b) trust in their treating doctor (88%), (c) desire to contribute to scientific research (62%) and (d) a belief that they may benefit from the therapy (39%). For these patients, 49% reported that the possibility of a repeat biopsy would not deter them from trial participation; whereas 11% said that it definitely would. Of the 6 patients that chose not to participate in a WOO trial the most common reasons included (a) travel or transportation issues (50%) and (b) lack of belief of potential benefit to them (33%). For these patients, when asked whether the participation of a cancer patient in the design of the WOO trial would change their mind, all reported that it would not make a difference. Conclusion: WOO trials are becoming increasingly common in oncology research. Understanding patient perspectives for WOO trial participation is useful to inform trial design and communication approaches in future WOO trial efforts. Citation Format: Vanessa Lopez Ozuna, Gregory R. Pond, John MS Bartlett, Lazlo Radvanyi, Melanie Spears, Teresa Petrocelli, Carol Gordon, Rebecca J. Rose, Angel Arnaout. Understanding Patient Perspectives on Window of Opportunity Clinical Trial Participation in Breast Cancer [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 P6-05-12.

Prognostic significance of germline BRCA mutations in patients with HER2-POSITIVE breast cancer

BackgroundHER2-positive breast cancers are rare amongst BRCA mutation carriers. No data exist regarding clinicopathological characteristics and prognosis of this subgroup of patients. Materials and methodsUsing a retrospective matched cohort design, we collected data from 700 women who were diagnosed with operable invasive breast cancer from January 2006 to December 2016 and were screened for germline BRCA mutations. Clinicopathological features and survival rates were analyzed by BRCA and HER2 status. ResultsOne hundred and fifteen HER2-positive/BRCA mutated cases were evaluated in comparison to the three control groups: HER2-positive/BRCA wild type (n = 129), HER2-negative/BRCA mutated (n = 222), HER2-negative/BRCA wild type (n = 234). HER2-positive breast cancers were more likely to have high histologic grade and high proliferation rate than HER2-negative neoplasms, regardless of BRCA mutation status. An interaction between BRCA mutations and HER2-positive status was found to correlate with worse survival after adjusting for prognostic variables (HR = 3.4; 95% CI: 1.3–16.7). ConclusionsCo-occurrence of BRCA mutations and HER2-positive status is a poor prognostic factor in patients with early or locally advanced breast cancer. This finding may be a proof of concept that a combined pharmacological intervention directed to these targets could be synergistic.

Five-year survival in luminal breast cancer patients: relation with intratumoral activity of proteasomes.

The purpose of the study was to analyze the relationship between the caspase-like (CL) and chymotrypsin-like (ChTL) activities of proteasomes and the 5-year overall and metastasis-free survival rates in patients with luminal breast cancer. The study included 117 patients with primary operable invasive breast cancer (T1-2N0-1M0). Tissue samples from breast cancer patients were obtained as a result of the radical mastectomy or breast conserving surgery, which was a first line of therapy. The ChTL and CL proteasomes activities in the tumor tissue and in the surrounding adjacent breast tissues were assessed using the fluorometric method. The coefficients of ChTL (cChTL) and CL (cCL) proteasomes activities were also determined. The coefficients were calculated as the ratio of the corresponding proteasomes activity in the tumor tissue to the surrounding adjacent breast tissues. Within 5 years of follow-up, hematogenous metastases occurred in 14% of patients with luminal A breast cancer, in 31% of patients with luminal B human epidermal growth factor receptor-2 (HER-2) negative and in 23% of patients with luminal B HER-2 positive breast cancers. The study protocol was approved by the Local Ethics Committee of the Cancer Research Institute of Tomsk National Research Medical Center. Written informed consent was obtained from all patients. An increase in the ChTL and CL proteasomes activities was shown in all studied molecular subtypes of breast cancer compared to adjacent tissues. It was found that the cChTL of >35.9 U/mg protein and the cCL of >2.21 in breast cancer patients were associated with the development of distant metastases. In patients with luminal A breast cancer, the 5-year metastasis-free survival rates were associated only with the value of cCL of proteasomes (log-rank test: P=0.008). In patients with luminal B HER-2 negative breast cancer, the 5-year metastasis-free survival rates were associated with the levels of ChTL and cCL proteasomes activities (log-rank test: P=0.02 and P=0.04, respectively). The data obtained on the correlation of 5-year metastasis-free survival rates with the level of proteasomes activities indicate the possibility of their use as additional prognostic criteria for breast cancer.

Abstract 5405: Expression of cathepsin D in early-stage breast cancer and its prognostic and predictive value

Abstract Purpose: Cathepsin D is a proteolytic enzyme that is normally localized in the lysosomes and is involved in the malignant progression of breast cancer. The expression of Cathepsin D is regulated by steroid hormones including oestrogen and growth factors. There are conflicting results between different studies regarding Cathepsin D significance as prognostic and predictor marker in breast cancer. Furthermore, Cathepsin D has not been recommended for clinical use by the American Society of Clinical Oncology because of insufficient evidence. This study was aimed to fill the gap in the lack of recent and large studies on prognostic significance of Cathepsin D expression by studying a large well-characterized series of primary breast cancer for cathepsin D expression using immunohistochemistry. Methods: Expression of Cathepsin D was assessed by immunohistochemical staining of tissue microarrays, in a large well-characterized series of early-stage operable breast cancer (n=954) from Nottingham Primary Breast Carcinoma Series between the period of 1988 and 1998 who underwent primary surgery. Correlation of cathepsin D expression with clinicopathological parameters and prognosis was evaluated. Results: Cathepsin D expression was positive in 28.8% (275/954) of breast cancer tumors. Positive expression of cathepsin D was significantly associated with high histological grade (p=0.007), pleomorphism (p=0.002), poor Nottingham Prognostic Index score (NPI) (p<0.002), recurrence (p=0.005) and distant metastasis (p<0.0001). Kaplan-Meier analysis showed that Cathepsin D expression was significantly associated with shorter breast cancer specific survival (BCSS) (p=0.001), higher risk of recurrence (p=0.001) and distant metastasis (p<0.0001). Cathepsin D positive tumors with ER positive staining who were treated with tamoxifen were associated with lower BCSS and higher risk of developing distant metastasis (p=0.001). Conclusion: This study shows Cathepsin D expression as a promising prognostic biomarker for early operable invasive breast cancer. Our results indicate that Cathepsin D expressing tumors are associated with shorter breast cancer specific survival and higher risk of recurrence and metastasis. Cathepsin D could be clinically useful to predict response to tamoxifen treatment. Targeting Cathepsin D either through inhibition of action or interference with the proteolytic pathway could be used to treat metastatic breast cancers expressing Cathepsin D. Citation Format: Inas M. Alhudiri, Christopher C. Nolan, Ian O. Ellis, Emad A. Rakha, Adam Elzagheid, Andrew R. Green, Caroline J. Chapman. Expression of cathepsin D in early-stage breast cancer and its prognostic and predictive value [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5405.

Intratumoral (IT) INT230-6 can cause tumor necrosis in vivo: Preliminary results of a phase II randomized presurgical window-of-opportunity study in early breast cancers (the INVINCIBLE study).

605 Background: The INVINCIBLE study is a randomized, Phase 2 presurgical Window-Of-Opportunity trial for IT INT230-6 (comprising VINblastine (VIN) Cisplatin (VIN)) evaluating clinical and BioLogical Effects in patients with early-stage operable Breast Cancer. INT230-6 also contains a dispersion enhancer molecule designed to facilitate diffusion of the cytotoxic agents into cancer cells and cause tumor necrosis. We have previously demonstrated that INT230-6 halts cancer cell replication and induces apoptosis while maturing dendritic cells and recruiting T-cells to the tumor microenvironment. In this trial, IT injections of INT230-6 are conducted to 1) exploit the potential of regional cytotoxic chemotherapy on breast cancer in vivo and 2) assess the potential for an immune response in the tumor microenvironment and host prior to surgical resection. Methods: Up to 90 women with newly diagnosed operable early-stage intermediate or high-grade T1-T2 invasive breast cancers are randomly allocated (2:1) prior to resection to IT injections of INT230-6, no treatment or saline sham. This study has two parts. Part I (N=29) was a randomized trial comparing 1-3 doses of INT230-6 injected weekly vs no treatment prior to surgery to evaluate safety, feasibility, and optimal drug dosing. Part II is a double-blinded randomized trial of up to 60 patients where patients will receive one IT dose of INT230-6 vs saline injection (2:1). The primary endpoint is to estimate the proportion of patients who achieve a complete cell cycle arrest post-surgery compared to the diagnosis biopsy. Secondary endpoints include an evaluation of the rate of pathological complete response, the percent of residual cancer, and safety. The study will also profile changes in CD4/CD8 and the T-cell repertoire. Results: Part I demonstrated feasibility, safety and tolerability of presurgical IT injections in breast cancer patients. Twenty patients with tumors ranging from 1-4.4cm were injected with at least one dose up to 48 hours prior to surgery. No surgeries were delayed or altered and the most common (>10%) AEs were injection site pain (100%), infusion site extravasation, injection site reaction and vomiting (10% each). Preliminary data show histologic evidence of up to 95% tumor necrosis in varying biologic subtypes and an increase in intratumoral TILs in injected tumors compared to controls. Part II is ongoing. Conclusions: Preliminary evidence shows that a single dose of INT230-6 can cause intratumoral necrosis and stimulate an immune response in breast cancers prior to surgery with minimal adverse effects and good tolerability. The results of Part II of the study will further evaluate the potential cytotoxic, immunomodulatory and other biologic effects of INT230-6 and its role as a potential cancer therapy in breast cancer patients awaiting surgery. Clinical trial information: NCT04781725.

TRIO-US B-12 TALENT: Phase II neoadjuvant trial evaluating trastuzumab deruxtecan with or without anastrozole for HER2-low, HR+ early-stage breast cancer.

TPS623 Background: Although patients with hormone receptor-positive (HR+)/HER2-negative breast cancer (BC) frequently experience disease response to neoadjuvant therapy, fewer than 10% achieve a pathologic complete response (pCR) with standard chemotherapy or endocrine therapy, even in combination with CDK4/6 inhibitors. Thus, finding more effective therapies for this disease remains an area of unmet need. HER2 amplification is a known driver of endocrine resistance and HER2 may be expressed at a low level (IHC 1+ or 2+) in approximately 60% of HR+ BC. Trastuzumab deruxtecan (DS-8201a, T-DXd) is a novel HER2-targeting antibody drug conjugate (ADC) that is FDA approved in the US for HER2-positive (with boxed warnings for interstitial lung disease) and has demonstrated promising clinical efficacy in HER2-low BC with an objective response rate of ̃37%. The aim of TALENT (TRIO-US B-12, NCT04553770) is to evaluate the clinical activity and safety of neoadjuvant T-DXd alone or in combination with endocrine therapy in patients with HR+/HER2-low early BC. Methods: This is an ongoing randomized, multicenter, open-label, two-stage, phase II neoadjuvant trial for participants with early stage, HR+, HER2-low (1+ or 2+/ISH- by IHC) BC. Eligible participants include men and women with previously untreated, operable invasive BC greater than 2.0 cm (cT2). Pts with recurrent, metastatic, or inflammatory BC are excluded. Pts are randomized 1:1 to receive six to eight cycles of T-DXd (5.4 mg/kg IV q21 days) alone or in combination with anastrozole AI (1 mg PO QD). Men and pre/peri menopausal women randomized to the AI arm also receive routine care GnRH agonist. Stratification factors include HER2 expression and menopausal status (men stratified as postmenopausal). Tumor tissue is taken at baseline, cycle 1 day 17-21, and at surgery. Blood samples are taken at 4 time points for biomarker analysis. The primary endpoint is pCR rate (breast and lymph node) at definitive surgery. In stage I, 58 participants will be randomized (29/arm). If >2 participants in an arm achieve pCR, that arm will expand (stage II) to enroll an additional 15 participants (total of 44/arm). A pCR rate of > 10% (5/44) would be considered favorable, warranting further evaluation in a larger trial. Other endpoints include safety, changes in Ki67 expression, Residual Cancer Burden index, biomarker analysis (including serial cfDNA analysis), and health-related quality of life. As of January 2022, 37 participants have enrolled, 24 have completed treatment, and 14 have had surgery. To our knowledge this is the first and only ongoing study evaluating T-DXd with or without endocrine therapy for HR+, HER2-low BC in the neoadjuvant setting. The study will shed light on clinical activity and biomarkers, which may guide larger confirmatory studies for this population. Clinical trial information: NCT04553770.

Abstract OT1-12-05: Phase II neoadjuvant trial evaluating trastuzumab deruxtecan with or without anastrozole for HER2-low, HR+ early stage breast cancer

Abstract Background Although patients with clinical response of hormone receptor-positive (HR+)/HER2-negative breast cancer (BC) frequently respond to neoadjuvant therapy, fewer than 10% of patients achieve a pathologic complete response (pCR) with standard chemotherapy or endocrine therapy, even in combination with targeted agents such as CDK4/6 inhibitors. Thus, finding more effective therapies for this disease remains an area of unmet need. HER2 amplification is a known driver of endocrine resistance and HER2 may be expressed at a low level (IHC 1+ or 2+) in up to 60% of HR+ BC. Trastuzumab deruxtecan (DS-8201a, T-DXd) is a novel HER2-targeting antibody drug conjugate (ADC) that is FDA approved for HER2-positive metastatic BC and has demonstrated promising clinical efficacy in HER2-low BC with an objective response rate of ~37%. The aim of TALENT (TRIO-US B-12) is to evaluate the clinical activity and toxicity of neoadjuvant T-DXd either alone or in combination with endocrine therapy in patients with HR+/HER2-low early BC. Methods TRIO-US B-12 TALENT (NCT04553770) is an ongoing randomized, multicenter, open-label, two-stage, phase II neoadjuvant trial for participants with early stage, HR+, HER2-low expressing (1+ or 2+ by IHC) BC. Eligible participants include men and women with previously untreated, operable invasive BC greater than 2.0 cm (cT2) in size. Pts with recurrent or metastatic BC, or inflammatory BC are excluded. Pts are randomized 1:1 to receive six cycles of T-DXd (5.4 mg/kg IV q21 days) either alone or in combination with anastrozole AI (1 mg PO QD). Men and pre/peri menopausal women randomized to the AI arm also receive standard of care GnRH agonist. Stratification factors include HER2 expression (1+ or 2+) and menopausal status (men stratified as post-menopausal). Tumor tissue is taken at baseline, cycle 1 day 17-21, and at surgery. Blood samples are taken at four time points for biomarker analysis. The primary endpoint is pCR rate (breast and lymph node) at definitive surgery. In stage I, 58 participants will be randomized (29/arm). If ≥2 participants in an arm achieve pCR, that arm will expand (stage II) to enroll an additional 15 participants (total of 44/arm). A pCR rate of >10% (5/44) would be considered favorable, warranting further evaluation of the treatment in a larger trial. Other endpoints include safety, changes in Ki67 expression, Residual Cancer Burden index, biomarker analysis (including serial cfDNA analysis), and health-related quality of life. As of June 2021, sixteen participants have enrolled. Conclusions To our knowledge this is the first and only ongoing study evaluating T-DXd with or without endocrine therapy for HR+, HER2-low breast cancer in the neoadjuvant setting. The study will shed light on clinical activity and biomarkers, which may guide larger confirmatory studies for patients with HR+, HER2-low early breast cancer. Citation Format: Sara Hurvitz, Aditya Bardia, Merry L. Tetef, Nicholas P. McAndrew, Steven Applebaum, Aashini K. Master, Maggie L. DiNome, Minna K. Lee, Evangelia Kirimis, David D. Kim, Lisa S. Wang, Kyle Greene, Vu Phan, Nihal Abdulla, David Chan, Laura M. Spring, Christine Kivork, James Chauv. Phase II neoadjuvant trial evaluating trastuzumab deruxtecan with or without anastrozole for HER2-low, HR+ early stage 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 OT1-12-05.

Defer surgery in operable breast cancer: how long is too long?

PurposeThe aim of this meta-analysis was to evaluate outcomes of surgery compared to primary endocrine therapy (PET) in patients with non-advanced, operable invasive breast cancer, and to determine if PET as initial therapy may safely postpone surgery.MethodsThe MEDLINE, EMBASE, PubMed, and Cochrane Library were searched from database inception to July 2020 to identify eligible studies. Inclusion criteria were experimental or observational studies with at least one arm treated with PET and a second arm treated with surgery with or without PET. Local recurrence or progression of disease was defined as either failure of non-operative management (tumor failing to decrease in size and/or continuous local or distant tumor growth) or relapse of breast tumor after tumor downsizing following PET. Effect estimates were expressed in hazard ratio and 95% confidence intervals (HR (95% CI)).ResultsThe analysis included six studies with 1499 unique patients. The median time to local progression of disease was 2.3 years. Patients treated with PET alone without surgery had a higher risk of local recurrence and or progression [HR (95% CI): 1.76 (1.33, 2.31); I2 = 84%; p < 0.001]. Patients treated with PET had more favorable outcomes in terms of overall survival [HR (95% CI): 1.24 (1.06, 1.46); I2 = 70%; p = 0.008] and less favorable outcomes in breast cancer-specific survival [HR (95% CI): 1.13 (0.98, 1.31); I2 = 41%; p = 0.10]. The risk of publication bias was assessed to be high in reporting local recurrence rates and low in reporting distant recurrence rates.ConclusionPET alone is inferior to surgery in the treatment of operable invasive breast cancer.However, it may be acceptable to postpone curative breast cancer surgery without risk of progression for 1.1 years or longer.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12282-021-01302-4.

De-escalation of five years adjuvant endocrine therapy duration in patients with ER-low positive (immunohistochemical 1% to 10%) early-stage breast cancer: A propensity-matched analysis from the prospectively maintained database.

538 Background: There are limited data on endocrine therapy benefits for patients with estrogen receptor (ER)-low positive breast cancer (staining 1% to 10% of tumor nuclei by immunohistology). We aimed to compare the effect of short-term 2-3 years versus standard 5 years of adjuvant endocrine therapy on survival outcomes in patients with ER-low positive early breast cancer. Methods: We used data from the prospectively maintained Breast Surgery Database of Fudan University Shanghai Cancer Center for this propensity-matched analysis. Women with ER-low positive, operable, and unilateral early-stage invasive ductal breast cancer were enrolled in this study. Patients with advanced disease, having received neoadjuvant chemotherapy or ovarian function suppression, or with unknown duration or longer than 5 years of adjuvant endocrine therapy were excluded. Enrolled patients were divided into three groups: received no endocrine therapy; received 2-3 years of endocrine therapy; and received approximately 5 years of endocrine therapy. The primary endpoint was disease-free survival (DFS). Multivariate Cox regression analysis and propensity score matching were performed to minimize bias. Hazard ratios (HR) with 95% CIs were calculated. Results: From 2012 to 2017, 634 patients with ER-low positive breast cancer in the database met the inclusion criteria. At a median follow-up of 60 months (interquartile range, 46-74), the 5-year DFS of the whole cohort was 84.9%, with 77.6% for patients who received no endocrine therapy (N = 89), 83.7% for patients who received 2-3 years endocrine treatment (N = 185), and 87.5% for patients who received 5 years endocrine therapy (N = 360). When compared with those receiving no endocrine therapy, patients receiving 5 years treatment was associated with a significantly improved DFS (HR, 0.55; 95% CI 0.32-0.95; P = 0.03); however, there was no significant difference in DFS between patients receiving 2-3 years and 5 years endocrine therapy (HR, 0.79; 95% CI, 0.48-1.28; P = 0.33). In the multivariate Cox regression analysis of the propensity score-matched samples of 360 patients, the DFS was not significantly better for patients who received 5 years of endocrine therapy than 2-3 years treatment (HR, 0.74; 95% CI 0.41-1.34; P = 0.32). An exploratory analysis of re-biopsy of the recurrence lesions indicated more than half of relapsed disease displayed ER-negative, and less than 5% lesions were proved to be ER ≥10% positive. Conclusions: Our data did not support the necessity of 5 years duration of endocrine therapy for patients with ER-low positive breast cancer. Short-term 2-3 years duration might be an alternative option. Further translational research on identifying endocrine-sensitive cases within ER-low positive patients is needed.

TRIO-US B-12 TALENT: Phase II neoadjuvant trial evaluating trastuzumab deruxtecan with or without anastrozole for HER2-low, HR+ early stage breast cancer.

TPS603 Background: Although patients with hormone receptor-positive (HR+)/HER2-negative breast cancer (BC) frequently respond clinically to neoadjuvant treatment, fewer than 10% achieve a pathologic complete response (pCR) with standard chemotherapy or endocrine therapy, even in combination with targeted agents such as CDK4/6 inhibitors. Thus, finding more effective therapies for this disease remains an area of unmet need. HER2 amplification is a known driver of endocrine resistance and HER2 protein may be expressed at a low level (IHC 1+ or 2+) in up to 60% of HR+ BC. Trastuzumab deruxtecan (DS-8201a, T-DXd) is a novel HER2-targeting antibody drug conjugate (ADC) that is FDA approved for HER2-positive metastatic BC and has demonstrated promising clinical efficacy in HER2-low BC with an objective response rate of ̃37%. The aim of TALENT (TRIO-US B-12) is to evaluate the clinical activity and toxicity of neoadjuvant T-DXd either alone or in combination with endocrine therapy in patients with HR+/HER2-low early BC. Methods: TRIO-US B-12 TALENT (NCT04553770) is an ongoing randomized, multicenter, open-label, two-stage, phase II neoadjuvant trial for participants with early stage, HR+, HER2-low expressing (1+ or 2+ by IHC) BC. Eligible participants include men and women with previously untreated, operable invasive BC greater than 2.0 cm (cT2) in size. Pts with recurrent or metastatic BC, or inflammatory BC are excluded. Pts are randomized 1:1 to receive six cycles of T-DXd (5.4 mg/kg IV q21 days) either alone or in combination with anastrozole (1 mg PO QD). Men and pre/peri menopausal women randomized to the anastrozole arm also receive standard of care GnRH agonist. Stratification factors include HER2 expression (1+ or 2+) and menopausal status. Tumor tissue is taken at baseline, cycle 1 day 17-21, and at surgery. Blood samples are taken at four time points for biomarker analysis. The primary endpoint is pCR rate (breast and lymph node) at definitive surgery. In stage I, 58 participants will be randomized (29/arm). If &gt;2 participants in an arm achieve pCR, that arm will expand (stage II) to enroll an additional 15 participants (total of 44/arm). A pCR rate of &gt;10% (5/44) would be considered favorable, warranting further evaluation of the treatment in a larger trial. Other endpoints include safety, changes in Ki67 expression, Residual Cancer Burden index, biomarker analysis (including serial cfDNA analysis), and health-related quality of life. As of January 2021, four participants have enrolled. Conclusions: To our knowledge this is the only ongoing study evaluating T-DXd with or without endocrine therapy for HR+, HER2-low breast cancer in the neoadjuvant setting. The study will shed light on clinical activity and biomarkers, which may guide larger confirmatory studies for patients with HR+, HER2-low early breast cancer. Clinical trial information: NCT04553770.

Stromal Cell-Derived Factor 1α (SDF-1α) in Invasive Breast Cancer: Associations with Vasculo-Angiogenic Factors and Prognostic Significance.

Simple SummaryThis prospective study was designed to examine the utility of stromal cell-derived factor 1α (SDF-1α) and selected vasculo-angiogenic parameters—vascular endothelial growth factor A (VEGF-A), the soluble forms of VEGF receptors type 1 and 2, and the number of circulating endothelial progenitor cells (circulating EPCs)—for estimating the probability of disease relapse in invasive breast cancer (IBrC) patients. Kaplan–Meier plots and log-rank and F Cox tests were used to determine the clinical outcomes in terms of disease-free survival (DFS). Patients with a combination of SDF-1α lower than 42 pg/dL and a number of circulating EPCs lower than 9.68 cells/µL had significantly shorter DFS (p = 0.0138); thus, the combination of these two factors shows strong diagnostic power for the prediction of disease relapse.(1) Background: Tumour angiogenesis is critical for the progression of neoplasms. A prospective study was designed to examine the utility of stromal cell-derived factor 1α (SDF-1α) and selected vasculo-angiogenic parameters for estimating the probability of disease relapse in 84 primary, operable invasive breast cancer (IBrC) patients (40 (48%) with stage IA and 44 (52%) with stage IIA and IIB). (2) Methods: We explored the prognostic value of the plasma levels of SDF-1α, vascular endothelial growth factor A (VEGF-A), the soluble forms of VEGF receptors type 1 and 2, and the number of circulating endothelial progenitor cells (circulating EPCs) in breast cancer patients. The median follow-up duration was 58 months, with complete follow-up for the first event. (3) Results: According to ROC curve analysis, the optimal cut-off point for SDF-1α (for discriminating between patients at high and low risk of relapse) was 42 pg/mL, providing 57% sensitivity and 75% specificity. Kaplan–Meier curves for disease-free survival (DFS) showed that concentrations of SDF-1α lower than 42 pg/dL together with a VEGFR1 lower than 29.86 pg/mL were significantly associated with shorter DFS in IBrC patients (p = 0.0381). Patients with both SDF-1α lower than 42 pg/dL and a number of circulating EPCs lower than 9.68 cells/µL had significantly shorter DFS (p = 0.0138). (4) Conclusions: Our results imply the clinical usefulness of SDF-1α, sVEGFR1 and the number of circulating EPCs as prognostic markers for breast cancer in clinical settings.

Accuracy of Magnetic Resonance Imaging–Guided Biopsy to Verify Breast Cancer Pathologic Complete Response After Neoadjuvant Chemotherapy

After neoadjuvant chemotherapy (NAC), pathologic complete response (pCR) is an optimal outcome and a surrogate end point for improved disease-free and overall survival. To date, surgical resection remains the only reliable method for diagnosing pCR. To evaluate the accuracy of magnetic resonance imaging (MRI)-guided biopsy for diagnosing a pCR after NAC compared with reference-standard surgical resection. Single-arm, phase 1, nonrandomized controlled trial in a single tertiary care cancer center from September 26, 2017, to July 29, 2019. The median follow-up was 1.26 years (interquartile range, 0.85-1.59 years). Data analysis was performed in November 2019. Eligible patients had (1) stage IA to IIIC biopsy-proven operable invasive breast cancer; (2) standard-of-care NAC; (3) MRI before and after NAC, with imaging complete response defined as no residual enhancement on post-NAC MRI; and (4) definitive surgery. Patients were excluded if they were younger than 18 years, had a medical reason precluding study participation, or had a prior history of breast cancer. Post-NAC MRI-guided biopsy without the use of intravenous contrast of the tumor bed before definitive surgery. The primary end point was the negative predictive value of MRI-guided biopsy, with true-negative defined as negative results of the biopsy (ie, no residual cancer) corresponding to a surgical pCR. Accuracy, sensitivity, positive predictive value, and specificity were also calculated. Two clinical definitions of pCR were independently evaluated: definition 1 was no residual invasive cancer; definition 2, no residual invasive or in situ cancer. Twenty of 23 patients (87%) had evaluable data (median [interquartile range] age, 51.5 [39.0-57.5] years; 20 women [100%]; 13 White patients [65%]). Of the 20 patients, pre-NAC median tumor size on MRI was 3.0 cm (interquartile range, 2.0-5.0 cm). Nineteen of 20 patients (95%) had invasive ductal carcinoma; 15 of 20 (75%) had stage II cancer; 11 of 20 (55%) had ERBB2 (formerly HER2 or HER2/neu)-positive cancer; and 6 of 20 (30%) had triple-negative cancer. Surgical pathology demonstrated a pCR in 13 of 20 (65%) patients and no pCR in 7 of 20 patients (35%) when pCR definition 1 was used. Results of MRI-guided biopsy had a negative predictive value of 92.8% (95% CI, 66.2%-99.8%), with accuracy of 95% (95% CI, 75.1%-99.9%), sensitivity of 85.8% (95% CI, 42.0%-99.6%), positive predictive value of 100%, and specificity of 100% for pCR definition 1. Only 1 patient had a false-negative MRI-guided biopsy result (surgical pathology showed <0.02 cm of residual invasive cancer). This study's results suggest that the accuracy of MRI-guided biopsy to diagnose a post-NAC pCR approaches that of reference-standard surgical resection. MRI-guided biopsy may be a viable alternative to surgical resection for this population after NAC, which supports the need for further investigation. ClinicalTrials.gov Identifier: NCT03289195.

Using Deep Learning to Improve Nonsystematic Viewing of Breast Cancer on MRI.

To investigate the feasibility of using deep learning to identify tumor-containing axial slices on breast MRI images. This IRB-approved retrospective study included consecutive patients with operable invasive breast cancer undergoing pretreatment breast MRI between January 1, 2014, and December 31, 2017. Axial tumor-containing slices from the first postcontrast phase were extracted. Each axial image was subdivided into two subimages: one of the ipsilateral cancer-containing breast and one of the contralateral healthy breast. Cases were randomly divided into training, validation, and testing sets. A convolutional neural network was trained to classify subimages into "cancer" and "no cancer" categories. Accuracy, sensitivity, and specificity of the classification system were determined using pathology as the reference standard. A two-reader study was performed to measure the time savings of the deep learning algorithm using descriptive statistics. Two hundred and seventy-three patients with unilateral breast cancer met study criteria. On the held-out test set, accuracy of the deep learning system for tumor detection was 92.8% (648/706; 95% confidence interval: 89.7%-93.8%). Sensitivity and specificity were 89.5% and 94.3%, respectively. Readers spent 3 to 45 seconds to scroll to the tumor-containing slices without use of the deep learning algorithm. In breast MR exams containing breast cancer, deep learning can be used to identify the tumor-containing slices. This technology may be integrated into the picture archiving and communication system to bypass scrolling when viewing stacked images, which can be helpful during nonsystematic image viewing, such as during interdisciplinary tumor board meetings.

Construction of the secondary care administrative records frailty (SCARF) index and validation on older women with operable invasive breast cancer in England and Wales: a cohort study

ObjectivesStudies that use national datasets to evaluate the management of older women with breast cancer are often constrained by a lack of information on patient fitness. This study constructed a...

Does Infiltrative Anesthesia Improve Post-operative Morbidity after Axillary Lymph Node Dissection in Patients of Breast Cancer? â A Prospective Study from a Tertiary Care Center in North India

Background: The role axillary lymph node dissection (ALND) in staging, prognostic assessment and local control in patients of breast cancer with clinically evident disease in the axilla is well established. ALND has its share of morbidity in the form of restriction of range of motion of arm, pain, paraesthesia and lymphedema influencing quality of life. This prospective study evaluates the effect of infiltrative anaesthesia injected along the nerve bundles exposed during ALND in reducing the restriction of range of motion of arm and pain scores following ALND. Methods: A total of 60 ALND in patients of operable invasive breast cancer were randomized in to two groups:- Group 1: The control group where patients of ALND were managed in the postoperative period with standard analgesia of injection acetaminophen 1 gm 8 hourly and early arm and shoulder movements from the evening of the procedure. Group 2: The test group had 5 ml of 0.125% Bupivaccaine injected each around the three nerve bundles exposed during ALND along with early arm and shoulder exercises and standard analgesia similar to the control group. Medical records of patients were analysed for age, laterality, clinical staging, histopathological parameters and surgical complications. Range of motion of ipsilateral at the shoulder and pain scores as recorded by visual analog scale (VAS) were objectively noted on day 0 to day 28 postoperatively at various intervals. Results: The range of motion at ipsilateral shoulder was measured by flexion, abduction and extension. The degrees of flexion and abduction were found to have statistically significant difference on Days 0, 3 and 7 in the test group in comparison to control group (p=0.001 for flexion on all Day 0,3 and 7 and p=0.009 for Day 0, p=0.001 for Day 3 and p<0.001 for Day 7 for abduction). Extension was better in the test group on Days 0 and 3 (p<0.001 and p=0.005 respectively). Pain scores assessed by VAS were significantly lower in test group when compared to control group on Days 0,1, 3 and 7 (p ≤ 0.01). There was no statistically significant difference in the restriction of flexion, extension and abduction and pain scores on Day 28 between the groups. Analgesia requirement was significantly reduced in the test group on days 0 and 1 (p ≤ 0.05). Conclusion: Infiltrative anaesthesia with 0.125% bupivaccaine along the nerve bundles exposed during ALND improves range of motion at shoulder and pain scores in the immediate postoperative period in patients of breast cancer.

Population-based Study of Prosigna-PAM50 and Outcome Among Postmenopausal Women With Estrogen Receptor-positive and HER2-negative Operable Invasive Lobular or Ductal Breast Cancer

PurposeThe Prosigna-PAM50 risk of recurrence (ROR) score has documented clinical utility for the prediction of 10-year distant recurrence (DR). The present study investigated the value of Prosigna-PAM50 for predicting 10-year DR and overall survival after 5 years of endocrine treatment for postmenopausal patients with invasive lobular carcinoma. Patients and MethodsUsing the Danish Breast Cancer Group database, we identified patients with a diagnosis from 2000 to 2003 of estrogen receptor-positive, human epidermal growth factor receptor 2-negative invasive ductal (n = 1570) or lobular (n = 341) cancer > 20 mm or 1 to 3 positive lymph nodes and applied multivariate Cox models. ResultsThe median follow-up for DR was 9.3 years and for overall survival 15.2 years. Of the 341 lobular and 1570 ductal cases, 140 (41%) and 349 (22%) were classified as low ROR, with a 10-year DR rate of 7.7% (95% confidence interval [CI], 3.7%-13.6%) and 3.5% (95% CI, 1.8%-6.2%), respectively. The 10-year DR rate for the intermediate ROR group for those with lobular cancer was 18% (95% CI, 10.1%-27.9%) compared with 9.7% (95% CI, 6.7%-13.4%) for those with ductal cancer. Luminal B tumors had a significantly worse outcome than luminal A tumors in both lobular (hazard ratio, 1.89; 95% CI, 1.03%-3.45%; P = .04) and ductal (hazard ratio, 3.18; 95% CI, 2.29%-4.43%; P < .0001) cancer. ConclusionProsigna PAM-50 provides significant prognostic information beyond the clinicopathologic factors in patients with invasive lobular breast cancer. Those with lobular cancer had worse 10-year DR rates compared with those with ductal cancer in the same ROR category. Our results could have an effect on the treatment decisions regarding the addition of chemotherapy for those in the intermediate ROR group.

Conditional Survival of female patients with operable invasive Breast Cancer in US: A population-based study.

Background: Conditional survival (CS) is used to describe the dynamic possibility of survival, considering the changes of death risk with time lapsing. This study aimed to estimate the conditional disease-specific survival (CDS) for the female with operable invasive breast cancer.Methods: The data was obtained from Surveillance, Epidemiology, and End Result Program of the National Cancer Institute. The hazard rate was calculated using kernel density smoothing method. The disease-specific survival (DSS) rates were estimated and compared using Kaplan-Meier method and log-rank test. The Cox regression model was used to adjust confounding factors. The CDS was calculated by CDS(y|x)=DSS(x + y)/DSS(x), where DSS(x) representatives the DSS at x year.Results: The 5-year, 10-year, and 15-year DSS was 88.7%, 82.0%, and 78.3%, respectively. The hazard rate after surgery increased initially and peaked at about 1.5 years, then decreased gradually. Meanwhile, the CDS decreased just after surgery then increased continuously, which showed a contrary trend with hazard rate. Patients with high risk factors had greater survival gap between cumulative DSS and CDS. The changing trend of CDS in patients with high risk factors was more significant, and the CDS gap between low-risk patients and high-risk patients gradually decreased over time.Conclusion: CS could provide a more precise long-term prognostic evaluation compared to traditional cumulative survival, especially for long-time survivors with high risk.

5P - Long-term prognostic effect of hormone receptor subtype on breast cancer

BackgroundTo determine the long-term prognostic role of hormone receptor subtype in breast cancer using the Surveillance, Epidemiology, and End Results (SEER) database. MethodsData of 810,587 female operable invasive breast cancer patients from SEER database with a mean follow-up period of 94.2 months (range, 0-311 months) were analyzed. Hormone receptor subtype was classified into four groups based on estrogen receptor (ER) and progesterone receptor (PR) statuses: ER(+)/PR(+), ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-). ResultsNumbers of subjects with ER(+)/PR(+), ER(+)/PR(-), ER(-)/PR(+), ER(-)/PR(-), and unknown were 496,279 (61.2%), 86,858 (10.7%), 11,545 (1.4%), 135,441 (16.7%), and 80,464 (9.9%), respectively. The ER(+)/PR(+) subtype showed the best breast cancer specific survival, followed by ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-) subtypes in order (all p < 0.001). Survival difference among hormone receptor subtypes was maintained in subgroup analysis according to anatomic stage, race, age group, and year of diagnosis. Hormone receptor subtype was a significant independent prognostic factor in multivariable analyses (p < 0.001). Hazard ratios of ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-) for breast cancer specific mortality risk were 1.419 (95% confidence interval [CI], 1.383-1.456), 1.630 (95% CI, 1.537-1.729), and 1.811 (95% CI, 1.773-1.848), respectively, with ER(+)/PR(+) as reference. ConclusionsHormone receptor subtype is a significant independent prognostic factor in female operable invasive breast cancer with long-term effect. The ER(+)/PR(+) subtype shows the most favorable prognosis, followed by ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-) subtypes in order. Prognostic impacts of hormone receptor subtypes are also maintained in subgroup analysis according to anatomic stage, race, age, and year of diagnosis. Legal entity responsible for the studyThe author. FundingHas not received any funding. DisclosureThe author has declared no conflicts of interest.