Timing of nivolumab with neoadjuvant carboplatin and paclitaxel for early triple-negative breast cancer (BCT1902/IBCSG 61-20; Neo-N): a non-comparative, open-label, randomised, phase 2 trial.

Background: The optimal scheduling of PD-1 inhibitors with neoadjuvant chemotherapy in patients with early triple-negative breast cancer is unknown. We aimed to investigate the activity of two differing schedules of neoadjuvant nivolumab initiation with 12 weeks of carboplatin and paclitaxel for this patient population.

Methods: Neo-N is an investigator-initiated, non-comparative, open-label, randomised, phase 2 trial conducted at 12 hospitals in Australia, one in New Zealand, and one in Italy.

Genomic Characterization and Prognostic Significance of Human Epidermal Growth Factor Receptor 2-Low, Hormone Receptor-Positive, Early Breast Cancers From the BIG 1-98 and SOFT Clinical Trials.

Purpose: To investigate whether hormone receptor-positive, human epidermal growth factor receptor 2-low (HR+HER2-low) versus HR+HER2-zero early breast cancers have distinct genomic and clinical characteristics.

Methods: This study included HR+, HER2-negative early breast cancers from patients enrolled in the phase III, randomized BIG 1-98 and SOFT clinical trials that had undergone tumor genomic sequencing. Tumors were classified HR+HER2-low if they had a centrally reviewed HER2 immunohistochemistry (IHC) score of 1+ or 2+ with negative in situ hybridization and HR+HER2-zero if they had an HER2 IHC score of 0.

Supervised Exercise for Patients With Metastatic Breast Cancer: A Cost-Utility Analysis Alongside the PREFERABLE-EFFECT Randomized Controlled Trial.

Purpose: To evaluate the cost utility of a 9-month supervised exercise program for patients with metastatic breast cancer (mBC), compared with control (usual care, supplemented with general activity advice and an activity tracker). Evidence on the cost-effectiveness of exercise for patients with mBC is essential for implementation in clinical practice and is currently lacking.

Methods: A cost-utility analysis was performed alongside the multinational PREFERABLE-EFFECT randomized controlled trial, conducted in 8 centers across Europe and Australia.

Sustained lymphocyte decreases after treatment for early breast cancer.

The role of adaptive immunity in long-term outcomes in early breast cancer is increasingly recognised. Standard (neo)adjuvant chemotherapy can have adverse effects on immune cells. We conducted a retrospective longitudinal study of full blood counts (FBC) of 200 patients receiving (neo)adjuvant chemotherapy for early breast cancer at a single institution.

Breast Cancer Index in Premenopausal Women With Early-Stage Hormone Receptor-Positive Breast Cancer.

Importance: Adjuvant ovarian function suppression (OFS) with oral endocrine therapy improves outcomes for premenopausal patients with hormone receptor-positive (HR+) breast cancer but adds adverse effects. A genomic biomarker for selecting patients most likely to benefit from OFS-based treatment is lacking.

Objective: To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer.

Supervised, structured and individualized exercise in metastatic breast cancer: a randomized controlled trial.

Physical exercise both during and after curative cancer treatment has been shown to reduce side effects. Evidence in the metastatic cancer setting is scarce, and interventions that improve health-related quality of life (HRQOL) are much needed for patients with metastatic breast cancer (MBC). The multinational randomized controlled PREFERABLE-EFFECT trial assessed the effects of exercise on fatigue and HRQOL in patients with MBC.

Denosumab Prevents Bone Loss and Microarchitectural Deterioration in Premenopausal Women With Breast Cancer Receiving Estradiol Suppression Therapy: A Randomized Controlled Trial.

Purpose: Suppression of ovarian function and aromatase inhibition (AI) increases disease-free survival in premenopausal women with estrogen receptor (ER)-positive early-stage breast cancer but accelerates bone loss. We therefore hypothesized that suppressing bone remodeling using denosumab (DMAB) would prevent bone loss in these women.

Methods: In a 12-month double-blind randomized trial, 68 women with ER-positive early-stage breast cancer commencing ovarian function suppression and AI were randomly assigned to 60 mg DMAB (n = 34) or placebo (PBO; n = 34) once every 6 months (at 0 and 6 months).

6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7).

This manuscript describes the Advanced Breast Cancer (ABC) international consensus guidelines updated at the last two ABC international consensus conferences (ABC 6 in 2021, virtual, and ABC 7 in 2023, in Lisbon, Portugal), organized by the ABC Global Alliance. It provides the main recommendations on how to best manage patients with advanced breast cancer (inoperable locally advanced or metastatic), of all breast cancer subtypes, as well as palliative and supportive care. These guidelines are based on available evidence or on expert opinion when a higher level of evidence is lacking.

Cardiometabolic Effects of Denosumab in Premenopausal Women With Breast Cancer Receiving Estradiol Suppression: RCT.

Context: Menopause is associated with changes in musculoskeletal, body composition, and metabolic parameters that may be amplified in premenopausal women receiving estradiol suppression for breast cancer. Denosumab offsets deleterious skeletal effects of estradiol suppression and has been reported to have effects on body composition and metabolic parameters in preclinical and observational studies, but evidence from double-blind randomized controlled trials is limited.

Objective: To assess the effect of denosumab on body composition and metabolic parameters.

BRCA1 and BRCA2 carriers with breast, ovarian and prostate cancer demonstrate a different pattern of metastatic disease compared with non-carriers: results from a rapid autopsy programme.

Aim: To catalogue and compare the pattern of metastatic disease in germline BRCA1/2 pathogenic mutation carriers and non-carriers with breast, ovarian and prostate cancer from a rapid autopsy programme.

Methods And Results: The number of metastases in the major body systems and the proportion of participants with metastases were documented in 50 participants (19 germline mutation carriers). Analysis was conducted on the participants' pattern of disease for the different cancers and mutation subgroups.

Selection of endpoints in breast cancer clinical trials: a qualitative study of key trial stakeholders.

Clinical trial endpoints are fundamental for evaluating the safety and efficacy of cancer therapies, yet it is not well understood how they are selected or the role of stakeholder groups in deciding endpoints. This study aimed to explore how clinical trial endpoints are selected in breast cancer trials of anti-cancer drugs through semi structured interviews with purposively selected stakeholders involved in breast cancer clinical trials (clinicians, consumers, pharmaceutical company representatives, and members of drug regulatory agencies). Participants were asked to describe the process of selecting trial endpoints.

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.

Role of Ovarian Suppression in Early Premenopausal Breast Cancer.

The benefit from removing ovaries to control premenopausal breast cancer growth was identified more than 100 years ago. Subsequent identification of estrogen receptor (ER) enabled targeting of this approach. Development of gonadotropin-releasing hormone agonists facilitated a reversible method of ovarian function suppression, suitable for young women with early breast cancer.

The Sleep, Cancer and Rest (SleepCaRe) Trial: Rationale and design of a randomized, controlled trial of cognitive behavioral and bright light therapy for insomnia and fatigue in women with breast cancer receiving chemotherapy.

Background: Insomnia and fatigue symptoms are common in breast cancer. Active cancer treatment, such as chemotherapy, appears to be particularly disruptive to sleep. Yet, sleep complaints often go unrecognised and under treated within routine cancer care.

Alpelisib Monotherapy for PI3K-Altered, Pretreated Advanced Breast Cancer: A Phase II Study.

Unlabelled: There is limited knowledge on the benefit of the α-subunit-specific PI3K inhibitor alpelisib in later lines of therapy for advanced estrogen receptor-positive (ER+) HER2- and triple-negative breast cancer (TNBC). We conducted a phase II multicohort study of alpelisib monotherapy in patients with advanced PI3K pathway mutant ER+HER2- and TNBC. In the intention-to-treat ER+ cohort, the overall response rate was 30% and the clinical benefit rate was 36%.

Understanding the barriers to, and facilitators of, ovarian toxicity assessment in breast cancer clinical trials.

Background: Detailed toxicity data are routinely collected in breast cancer (BC) clinical trials. However, ovarian toxicity is infrequently assessed, despite the adverse impacts on fertility and long-term health from treatment-induced ovarian insufficiency.

Objectives: To determine the barriers to and facilitators of ovarian toxicity assessment in BC trials of anti-cancer drugs.

Mechanisms of Cognitive Behavioral Therapy and Light Therapy for Cancer-Related Insomnia: A Randomized Clinical Trial during Chemotherapy for Breast Cancer.

Study Objectives: This study aimed to investigate the mechanisms of a combined brief cognitive behavioral plus bright light therapy (CBT-I+Light) in women receiving chemotherapy.

Methods: Women (N = 101) were randomly assigned to CBT-I+Light or treatment as usual plus relaxation audios (TAU+). Participants completed sleep diaries and wore an actigraph during the 6-week intervention period.

Tumor infiltrating lymphocyte stratification of prognostic staging of early-stage triple negative breast cancer.

The importance of integrating biomarkers into the TNM staging has been emphasized in the 8 Edition of the American Joint Committee on Cancer (AJCC) Staging system. In a pooled analysis of 2148 TNBC-patients in the adjuvant setting, TILs are found to strongly up and downstage traditional pathological-staging in the Pathological and Clinical Prognostic Stage Groups from the AJJC 8 edition Cancer Staging System. This suggest that clinical and research studies on TNBC should take TILs into account in addition to stage, as for example patients with stage II TNBC and high TILs have a better outcome than patients with stage I and low TILs.

The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group.

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis.

Light enhanced cognitive behavioral therapy for insomnia and fatigue during chemotherapy for breast cancer: a randomized controlled trial.

Study Objectives: Sleep problems are common during chemotherapy for breast cancer (BC). We evaluated whether combined brief cognitive behavioral and bright light therapy (CBT-I + Light) is superior to treatment as usual with relaxation audio (TAU+) for insomnia symptoms and sleep efficiency (primary outcomes).

Methods: We randomized women receiving intravenous chemotherapy, stratified by tumor stage and insomnia severity index, to 6-week CBT-I + Light or TAU+.

Heparanase: a potential marker of worse prognosis in estrogen receptor-positive breast cancer.

Heparanase promotes tumor growth in breast tumors. We now evaluated heparanase protein and gene-expression status and investigated its impact on disease-free survival in order to gain better insight into the role of heparanase in ER-positive (ER+) breast cancer prognosis and to clarify its role in cell survival following chemotherapy. Using pooled analysis of gene-expression data, we found that heparanase was associated with a worse prognosis in estrogen receptor-positive (ER+) tumors (log-rank p < 10) and predictive to chemotherapy resistance (interaction p = 0.