Factors influencing 5-year persistence to adjuvant endocrine therapy in young women with breast cancer.

Purpose: Although younger age has been negatively associated with persistence to adjuvant endocrine therapy (ET), factors contributing to non-persistence remain poorly understood. We assessed factors associated with non-persistence to ET and described the 5-year trajectories of quality of life (QoL) and symptoms in young women (≤40 years) with hormone receptor-positive breast cancer (BC).

Methods: We retrieved data on clinical characteristics and non-persistence from the medical annual records in the European cohort of the "Helping Ourselves, Helping Others: The Young Women's BC Study" (IBCSG 43-09 HOHO).

Fertility Preservation and Assisted Reproduction in Patients With Breast Cancer Interrupting Adjuvant Endocrine Therapy to Attempt Pregnancy.

Purpose: We investigated time to pregnancy, efficacy and safety of fertility preservation, and assisted reproductive technologies (ARTs) in women with early hormone receptor-positive breast cancer (BC) desiring future pregnancy.

Patients And Methods: POSITIVE is an international, single-arm, prospective trial, in which 518 women temporarily interrupted adjuvant endocrine therapy to attempt pregnancy. We evaluated menstruation recovery and factors associated with time to pregnancy and investigated if ART use was associated with achieving pregnancy.

Interrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer.

Background: Prospective data on the risk of recurrence among women with hormone receptor-positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking.

Methods: We conducted a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy.

Genomic characterisation of hormone receptor-positive breast cancer arising in very young women.

Background: Very young premenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained.

Patients And Methods: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the Suppression of Ovarian Function Trial (SOFT) to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1276 patients (deep targeted sequencing, n = 1258; whole-exome sequencing in a young-age, case-control subsample, n = 82).

Adjuvant Exemestane With Ovarian Suppression in Premenopausal Breast Cancer: Long-Term Follow-Up of the Combined TEXT and SOFT Trials.

JCO The combined analysis of SOFT-TEXT compared outcomes in 4,690 premenopausal women with estrogen/progesterone receptor-positive (ER/PgR+) early breast cancer randomly assigned to 5 years of exemestane + ovarian function suppression (OFS) versus tamoxifen + OFS. After a median follow-up of 9 years, exemestane + OFS significantly improved disease-free survival (DFS) and distant recurrence-free interval (DRFI), but not overall survival, compared with tamoxifen + OFS. We now report DFS, DRFI, and overall survival after a median follow-up of 13 years.

Adjuvant Endocrine Therapy in Premenopausal Breast Cancer: 12-Year Results From SOFT.

JCO The Suppression of Ovarian Function Trial (SOFT; ClinicalTrials.gov identifier: NCT00066690) randomly assigned premenopausal women with hormone receptor-positive breast cancer to 5 years of adjuvant tamoxifen, tamoxifen plus ovarian function suppression (OFS), or exemestane plus OFS. The primary analysis compared disease-free survival (DFS) between tamoxifen plus OFS versus tamoxifen alone; exemestane plus OFS versus tamoxifen was a secondary objective.

Moderate penetrance genes complicate genetic testing for breast cancer diagnosis: ATM, CHEK2, BARD1 and RAD51D.

Breast cancer risk associated with germline likely pathogenic/pathogenic variants (PV) varies by gene, often by penetrance (high >50% or moderate 20-50%), and specific locus. Germline PVs in BRCA1 and BRCA2 play important roles in the development of breast and ovarian cancer in particular, as well as in other cancers such as pancreatic and prostate cancers and melanoma. Recent studies suggest that other cancer susceptibility genes, including ATM, CHEK2, PALB2, RAD51C and RAD51D confer differential risks of breast and other specific cancers.

Employment trajectories of young women with breast cancer: an ongoing prospective cohort study in Italy and Switzerland.

Purpose: Despite extensive research on cancer and work-related outcomes, evidence from longitudinal cohort studies is limited, especially in young women with breast cancer (BC). We aimed to investigate employment trajectories in young BC survivors and to identify potential factors associated with changes in work activity.

Methods: The HOHO European prospective multicenter cohort study enrolled 300 young women (≤ 40 years) with newly diagnosed BC.

Who are the women who enrolled in the POSITIVE trial: A global study to support young hormone receptor positive breast cancer survivors desiring pregnancy.

Background: Premenopausal women with early hormone-receptor positive (HR+) breast cancer receive 5-10 years of adjuvant endocrine therapy (ET) during which pregnancy is contraindicated and fertility may wane. The POSITIVE study investigates the impact of temporary ET interruption to allow pregnancy.

Methods: POSITIVE enrolled women with stage I-III HR + early breast cancer, ≤42 years, who had received 18-30 months of adjuvant ET and wished to interrupt ET for pregnancy.

Continuous versus intermittent extended adjuvant letrozole for breast cancer: final results of randomized phase III SOLE (Study of Letrozole Extension) and SOLE Estrogen Substudy.

Background: Late recurrences in postmenopausal women with hormone receptor-positive breast cancers remain an important challenge. Avoidance or delayed development of resistance represents the main objective in extended endocrine therapy (ET). In animal models, resistance was reversed with restoration of circulating estrogen levels during interruption of letrozole treatment.

Biological and clinical features of triple negative Invasive Lobular Carcinomas of the breast. Clinical outcome and actionable molecular alterations.

Background: We report here for the first time, a comprehensive characterization of biological and clinical features of early-stage triple negative Invasive Lobular Carcinomas(TN-ILCs) METHODS: We analyzed all consecutive patients with early-stage TN-ILC operated at two reference cancer-centers between 1994 and 2012. Primary objective was to assess the invasive disease-free survival(iDFS). Co-primary objective was to assess biological features of TN-ILCs, including molecular intrinsic subtypes based on PAM-50 assay, expression of androgen receptor (AR) and mutational status of ERBB2-gene.

Sex-Based Dimorphism of Anticancer Immune Response and Molecular Mechanisms of Immune Evasion.

Purpose: We previously demonstrated that sex influences response to immune checkpoint inhibitors. In this article, we investigate sex-based differences in the molecular mechanisms of anticancer immune response and immune evasion in patients with NSCLC.

Experimental Design: We analyzed (i) transcriptome data of 2,575 early-stage NSCLCs from seven different datasets; (ii) 327 tumor samples extensively characterized at the molecular level from the TRACERx lung study; (iii) two independent cohorts of 329 and 391 patients, respectively, with advanced NSCLC treated with anti-PD-1/anti-PD-L1 drugs.

Clinical behavior of recurrent hormone receptor-positive breast cancer by adjuvant endocrine therapy within the Breast International Group 1-98 clinical trial.

Background: Endocrine therapy resistance is a major cause of distant recurrence (DR) in hormone receptor-positive breast cancer. This study evaluated differences in survival after DR in patients treated with different adjuvant endocrine therapy regimens in the Breast International Group (BIG) 1-98 trial.

Methods: BIG 1-98 compared 5 years of adjuvant treatment among 4 arms: tamoxifen (T), letrozole (L), tamoxifen followed by letrozole (TL), and letrozole followed by tamoxifen (LT).

Cumulative incidence of cardiovascular events under tamoxifen and letrozole alone and in sequence: a report from the BIG 1-98 trial.

Background: Compared to tamoxifen, adjuvant treatment with aromatase inhibitors improves disease outcomes of postmenopausal women with hormone receptor-positive early breast cancer. In the international, randomized, double-blind BIG 1-98 trial, 8010 women were randomized to receive tamoxifen, letrozole, or sequential use of the agents for 5 years. With a focus on switching between agents, we investigated cardiovascular events over the entire 5-year treatment period.

Genomic Aberrations and Late Recurrence in Postmenopausal Women with Hormone Receptor-positive Early Breast Cancer: Results from the SOLE Trial.

Purpose: Women with hormone receptor-positive early breast cancers have a persistent risk of relapse and biomarkers for late recurrence are needed. We sought to identify tumor genomic aberrations associated with increased late-recurrence risk.

Experimental Design: In a secondary analysis of Study of Letrozole Extension trial, a case-cohort-like sampling selected 598 primary breast cancers for targeted next-generation sequencing analysis of gene mutations and copy-number gains (CNGs).

Treatment-induced symptoms, depression and age as predictors of sexual problems in premenopausal women with early breast cancer receiving adjuvant endocrine therapy.

Purpose: Sexual dysfunction is an important concern of premenopausal women with early breast cancer. We investigated predictors of sexual problems in two randomized controlled trials.

Methods: A subset of patients enrolled in TEXT and SOFT completed global and symptom-specific quality-of-life indicators, CES-Depression and MOS-Sexual Problems measures at baseline, six, 12 and 24 months.

Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer.

Background: Ipsilateral breast cancer recurrence (IBTR) occurs in about 7% of patients with primary invasive breast tumor. Salvage mastectomy and breast reconstruction are often discussed and latissimus dorsi (LD) flap is frequently proposed.

Methods: We retrospectively investigated 111 consecutive locally relapsing patients who underwent salvage mastectomy and immediate LD reconstruction.

Correction: Quality of life under extended continuous versus intermittent adjuvant letrozole in lymph node-positive, early breast cancer patients: the SOLE randomised phase 3 trial.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

European Guidelines on the Organisation of Breast Centres and Voluntary Certification Processes.

Background: EUSOMA undertook the commitment of defining the requirements for a specialist breast centre, which has become the reference document for the implementation of breast centres.

Summary: The EUSOMA requirements for a specialist breast centre give clear indications regarding the requisite caseload, dedicated team composition (core and non-core team), organisation, availability of services and equipment throughout the patient pathway, quality control, and application of a multidisciplinary approach. The minimum number of cases is 150 newly diagnosed breast cancer cases per year.

Endocrine-responsive lobular carcinoma of the breast: features associated with risk of late distant recurrence.

Background: Invasive lobular carcinomas (ILCs) account for 10-15% of all breast cancers. They are characterized by an elevated endocrine responsiveness and by a long lasting risk of relapse over time. Here we report for the first time an analysis of clinical and pathological features associated with the risk of late distant recurrence in ILCs.

Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT.

Purpose: The Tamoxifen and Exemestane Trial (TEXT)/Suppression of Ovarian Function Trial (SOFT) showed superior outcomes for premenopausal women with hormone receptor (HR)-positive breast cancer treated with adjuvant exemestane plus ovarian function suppression (OFS) or tamoxifen plus OFS versus tamoxifen alone. We previously reported the magnitude of absolute improvements in freedom from any recurrence across a continuous, composite measure of recurrence risk to tailor decision making. With longer follow-up, we now focus on distant recurrence.

Long-term responders to trastuzumab monotherapy in first-line HER-2+ advanced breast cancer: characteristics and survival data.

Background: The impact of HER2-targeted therapy alone followed by the addition of chemotherapy at disease progression (PD) versus upfront combination was investigated by the SAKK 22/99 trial. The aim of this exploratory analysis of the SAKK 22/99 trial was to characterize the specific subset of patients deriving long-term benefit from trastuzumab monotherapy alone and to identify potential predictive factors of long-term response.

Methods: This is an unplanned post-hoc analysis of patients randomized to Arm A (trastuzumab monotherapy).

Fertility concerns, preservation strategies and quality of life in young women with breast cancer: Baseline results from an ongoing prospective cohort study in selected European Centers.

Objectives: Most research addressing needs and concerns of young patients with breast cancer (≤40 years) is retrospective. The HOHO European protocol is a prospective multicenter cohort study of young women with newly diagnosed breast cancer, about fertility, psychosocial and quality of life concerns. Here we report the baseline data and focus on predictors of fertility concerns.

Sex-Based Heterogeneity in Response to Lung Cancer Immunotherapy: A Systematic Review and Meta-Analysis.

Background: We previously showed that therapy with anti-checkpoints T-lymphocyte-associated protein 4 (anti-CTLA-4) or antiprogrammed cell death protein 1 (anti-PD-1) agents was more effective for men as compared with women. However, because the sex-dimorphism of the immune system is complex, involving multiple elements of immune responses, it is possible that women could derive larger benefit than men from strategies other than therapy with immune checkpoint inhibitors (ICIs) alone. Here we investigated whether women could derive larger benefit than men from the combination of chemotherapy and anti-PD-1 or anti-PD-L1.