A Phase I Trial of Alpelisib Combined With Capecitabine in Patients With HER2-Negative Metastatic Breast Cancer.

Background: Alpelisib is an oral α-specific class I PI3K inhibitor approved in combination with fulvestrant for the treatment of PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. The tolerability of this drug with the oral chemotherapy capecitabine is unknown.

Patients And Methods: This phase I trial evaluated the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of alpelisib (250 mg or 300 mg daily for 3-weeks) with capecitabine (1000 mg/m twice daily for 2-weeks followed by a 1-week rest period) in patients with metastatic HER2-negative breast cancer, regardless of PIK3CA mutation status.

Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab for Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results and Correlative Analyses From ATEMPT.

Purpose: Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need.

Methods: In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1.

Identifying homologous recombination deficiency in breast cancer: genomic instability score distributions differ among breast cancer subtypes.

Purpose: A 3-biomarker homologous recombination deficiency (HRD) score is a key component of a currently FDA-approved companion diagnostic assay to identify HRD in patients with ovarian cancer using a threshold score of ≥ 42, though recent studies have explored the utility of a lower threshold (GIS ≥ 33). The present study evaluated whether the ovarian cancer thresholds may also be appropriate for major breast cancer subtypes by comparing the genomic instability score (GIS) distributions of BRCA1/2-deficient estrogen receptor-positive breast cancer (ER + BC) and triple-negative breast cancer (TNBC) to the GIS distribution of BRCA1/2-deficient ovarian cancer.

Methods: Ovarian cancer and breast cancer (ER + BC and TNBC) tumors from ten study cohorts were sequenced to identify pathogenic BRCA1/2 mutations, and GIS was calculated using a previously described algorithm.

Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial.

Background: We aimed to report on long-term outcomes of patients with small, node-negative, HER2-positive breast cancer treated with adjuvant paclitaxel and trastuzumab and to establish potential biomarkers to predict prognosis.

Methods: In this open-label, single-arm, phase 2 study, patients aged 18 years or older, with small (≤3 cm), node-negative, HER2-positive breast cancer, and an Eastern Cooperative Oncology Group performance status of 0-1, were recruited from 16 institutions in 13 cities in the USA. Eligible patients were given intravenous paclitaxel (80 mg/m) with intravenous trastuzumab (loading dose of 4 mg/kg, subsequent doses 2 mg/kg) weekly for 12 weeks, followed by trastuzumab (weekly at 2 mg/kg or once every 3 weeks at 6 mg/kg) for 40 weeks to complete a full year of trastuzumab.

Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis.

The AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and global DNA methylation microarrays. Expression subtype changes were observed in ~30% of samples and were coincident with DNA clonality shifts, especially involving HER2.

Predictors of long-term durable response in de novo HER2-positive metastatic breast cancer and the real-world treatment experience at two institutions.

Purpose: HER2-directed therapies enable some patients with de novo HER2+ metastatic breast cancer (MBC) to achieve long-term, durable responses (DR). Expert opinion dictates indefinite HER2-directed therapies for patients who achieve DRs, but real-world examples of this practice are lacking in the literature. Patient factors that predict DR continue to be elucidated.

The Phase II MutHER Study of Neratinib Alone and in Combination with Fulvestrant in HER2-Mutated, Non-amplified Metastatic Breast Cancer.

Purpose: HER2 mutations (HER2mut) induce endocrine resistance in estrogen receptor-positive (ER+) breast cancer.

Patients And Methods: In this single-arm multi-cohort phase II trial, we evaluated the efficacy of neratinib plus fulvestrant in patients with ER+/HER2mut, HER2 non-amplified metastatic breast cancer (MBC) in the fulvestrant-treated (n = 24) or fulvestrant-naïve cohort (n = 11). Patients with ER-negative (ER-)/HER2mut MBC received neratinib monotherapy in an exploratory ER- cohort (n = 5).

Analysis of Sociodemographic, Clinical, and Genomic Factors Associated With Breast Cancer Mortality in the Linked Surveillance, Epidemiology, and End Results and Medicare Database.

Importance: Understanding interactions among health service, sociodemographic, clinical, and genomic factors in breast cancer disparities research has been limited by a disconnect between health services and basic biological approaches.

Objective: To describe the first linkage of Surveillance, Epidemiology, and End Results (SEER)-Medicare data to physical tumor samples and to investigate the interaction among screening detection, socioeconomic status, tumor stage, tumor biology, and breast cancer outcomes within a single context.

Design, Setting, And Participants: This population-based cohort study used tumor specimen blocks from a subset of women aged 66 to 75 years with newly diagnosed nonmetastatic, estrogen receptor-positive invasive breast cancer from January 1, 1993, to December 31, 2007.

Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients.

Circulating tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). The CTC-endocrine therapy index (CTC-ETI), consisting of CTC-ER (estrogen receptor), BCL2, human epidermal growth factor receptor (HER2), and Ki67 expression, might predict resistance to endocrine therapy (ET) in patients with ER-positive MBC. One hundred twenty-one patients with ER-positive/HER2-negative MBC initiating a new ET after ≥1 lines of ET were enrolled in a prospective, multi-institutional clinical trial.

Patient-reported causes of distress predict disparities in time to evaluation and time to treatment after breast cancer diagnosis.

Background: We examined whether the National Comprehensive Cancer Network distress thermometer (DT), a patient-reported outcome measure, could be used to identify levels and causes of distress associated with racial/ethnic disparities in time to care among patients with breast cancer.

Methods: We identified women aged ≥18 years with stage 0-IV breast cancer who were diagnosed in a single health system between January 2014 and July 2016. The baseline visit was defined as the first postdiagnosis, pretreatment clinical evaluation.

TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes.

Purpose: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) in germline (g)/ mutation carriers. Olaparib Expanded, an investigator-initiated, phase II study, assessed olaparib response in patients with MBC with somatic (s)/ mutations or g/s mutations in homologous recombination (HR)-related genes other than 2.

Methods: Eligible patients had MBC with measurable disease and germline mutations in non-/ HR-related genes (cohort 1) or somatic mutations in these genes or / (cohort 2).

TBCRC 030: a phase II study of preoperative cisplatin versus paclitaxel in triple-negative breast cancer: evaluating the homologous recombination deficiency (HRD) biomarker.

Background: Cisplatin and paclitaxel are active in triple-negative breast cancer (TNBC). Despite different mechanisms of action, effective predictive biomarkers to preferentially inform drug selection have not been identified. The homologous recombination deficiency (HRD) assay (Myriad Genetics, Inc.

Quantitative assessment of distant recurrence risk in early stage breast cancer using a nonlinear combination of pathological, clinical and imaging variables.

Use of genomic assays to determine distant recurrence risk in patients with early stage breast cancer has expanded and is now included in the American Joint Committee on Cancer staging manual. Algorithmic alternatives using standard clinical and pathology information may provide equivalent benefit in settings where genomic tests, such as OncotypeDx, are unavailable. We developed an artificial neural network (ANN) model to nonlinearly estimate risk of distant cancer recurrence.

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.

Several new systemic therapy options have become available for patients with metastatic breast cancer, which have led to improvements in survival. In addition to patient and clinical factors, the treatment selection primarily depends on the tumor biology (hormone-receptor status and HER2-status). The NCCN Guidelines specific to the workup and treatment of patients with recurrent/stage IV breast cancer are discussed in this article.

TBCRC 031: Randomized Phase II Study of Neoadjuvant Cisplatin Versus Doxorubicin-Cyclophosphamide in Germline Carriers With HER2-Negative Breast Cancer (the INFORM trial).

Purpose: Platinum compounds have activity in triple-negative breast cancer (TNBC) in germline mutation carriers ( carriers). Limited data exist for estrogen receptor (ER)-positive (+) breast cancer among carriers. INFORM is a randomized, multicenter, phase II trial comparing pathologic complete response (pCR) rates (ypT0/is, N0) after neoadjuvant single-agent cisplatin (CDDP) versus doxorubicin-cyclophosphamide (AC) in carriers with stage I-III human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer.

Background: Patients with chemotherapy refractory metastatic colorectal cancer (CRC) have a poor prognosis and limited therapeutic options. In this phase Ib/II clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RPTD) for the combination of capecitabine and ziv-aflibercept, and then we evaluated the efficacy of the combination in patients with chemotherapy refractory metastatic CRC.

Methods: All patients were required to have a Karnofsky Performance Status > 70% and adequate organ function.

Perspectives on Inflammatory Breast Cancer (IBC) Research, Clinical Management and Community Engagement from the Duke IBC Consortium.

Inflammatory breast cancer (IBC) is an understudied and aggressive form of breast cancer with a poor prognosis, accounting for 2-6% of new breast cancer diagnoses but 10% of all breast cancer-related deaths in the United States. Currently there are no therapeutic regimens developed specifically for IBC, and it is critical to recognize that all aspects of treating IBC - including staging, diagnosis, and therapy - are vastly different than other breast cancers. In December 2014, under the umbrella of an interdisciplinary initiative supported by the Duke School of Medicine, researchers, clinicians, research administrators, and patient advocates formed the Duke Consortium for IBC to address the needs of patients in North Carolina (an ethnically and economically diverse state with 100 counties) and across the Southeastern United States.

The effect of treatment on patient-reported distress after breast cancer diagnosis.

Background: The National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) uses a 10-point scale (in which 0 indicates no distress and 10 indicates extreme distress) to measure patient-reported distress. In the current study, the authors sought to examine the relationship between treatment and NCCN DT scores in patients with breast cancer over time.

Methods: The authors included women aged ≥18 years who were diagnosed with stage 0 to stage IV breast cancer (according to the seventh edition of the American Joint Commission on Cancer staging system) at a 3-hospital health system from January 2014 to July 2016.

Local-regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial).

Purpose: Women with HER2-positive breast cancer treated prior to effective anti-HER2 therapy have higher rates of local-regional recurrence (LRR) than those with HER2-negative disease. Effective systemic therapy, however, has been shown to decrease LRR. This study examines LRR in women with HER2-positive breast cancer treated on a single-arm prospective multicenter trial of adjuvant trastuzumab (H) and paclitaxel (T).

Partner status moderates the relationships between sexual problems and self-efficacy for managing sexual problems and psychosocial quality-of-life for postmenopausal breast cancer survivors taking adjuvant endocrine therapy.

Objective: Past studies indicate that >90% of breast cancer survivors taking adjuvant endocrine therapy (AET) experience menopausal symptoms including sexual problems (eg, vaginal dryness, dyspareunia); however, research examining the impact of these problems on quality-of-life is limited. This cross-sectional study examined (1) the impact of sexual problems and self-efficacy for coping with sexual problems (sexual self-efficacy) on quality-of-life (ie, psychosocial quality-of-life and sexual satisfaction), and (2) partner status as a moderator of these relationships.

Methods: Postmenopausal breast cancer survivors taking AET completed measures of sexual problems (Menopause-Specific Quality-of-Life [MENQOL] sexual subscale], sexual self-efficacy, psychosocial quality-of-life (MENQOL psychosocial subscale), and sexual satisfaction (Functional Assessment of Cancer Therapy-General item).

NCCN Guidelines Insights: Breast Cancer, Version 3.2018.

These NCCN Guidelines Insights highlight the updated recommendations for use of multigene assays to guide decisions on adjuvant systemic chemotherapy therapy for women with hormone receptor-positive, HER2-negative early-stage invasive breast cancer. This report summarizes these updates and discusses the rationale behind them.

The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial.

Background: Previous data suggest that the immune microenvironment plays a critical role in human epidermal growth factor receptor 2 (HER2) -positive breast cancer; however, there is little known about the immune profiles of small HER2-positive tumors. In this study, we aimed to characterize the immune microenvironment of small HER2-positive breast cancers included in the Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer (APT) trial and to correlate the immune markers with pathological and molecular tumor characteristics.

Patients And Methods: The APT trial was a multicenter, single-arm, phase II study of paclitaxel and trastuzumab in patients with node-negative HER2-positive breast cancer.