Final Results From the Randomized Phase III ASCENT Clinical Trial in Metastatic Triple-Negative Breast Cancer and Association of Outcomes by Human Epidermal Growth Factor Receptor 2 and Trophoblast Cell Surface Antigen 2 Expression.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Sacituzumab govitecan (SG), a first-in-class anti-trophoblast cell surface antigen 2 (Trop-2) antibody-drug conjugate, demonstrated superior efficacy over single-agent chemotherapy (treatment of physician's choice [TPC]) in patients with metastatic triple-negative breast cancer (mTNBC) in the international, multicenter, phase III ASCENT study.Patients were randomly assigned 1:1 to receive SG or TPC until unacceptable toxicity/progression. Final efficacy secondary end point analyses and post hoc analyses of outcomes stratified by Trop-2 expression and human epidermal growth factor receptor 2 status are reported. Updated safety analyses are provided.In this final analysis, SG (n = 267) improved median progression-free survival (PFS; 4.8 v 1.7 months; hazard ratio (HR), 0.41 [95% CI, 0.33 to 0.52]) and median overall survival (OS; 11.8 v 6.9 months; HR, 0.51 [95% CI, 0.42 to 0.63]) over TPC (n = 262). SG improved PFS over TPC in each Trop-2 expression quartile (n = 168); a trend was observed for improved OS across quartiles. Overall, SG had a manageable safety profile, with ≤5% of treatment-related discontinuations because of adverse events and no treatment-related deaths. The safety profile was consistent across all subgroups.These data confirm the clinical benefit of SG over chemotherapy, reinforcing SG as an effective treatment option in patients with mTNBC in the second line or later.

Molecular imaging predicts lack of T-DM1 response in advanced HER2-positive breast cancer (final results of ZEPHIR trial).

Efficacy of the human epidermal growth factor receptor (HER)2-targeting trastuzumab emtansine (T-DM1) in breast cancer (BC) relies on HER2 status determined by immunohistochemistry or fluorescence in-situ hybridization. Heterogeneity in HER2 expression, however, generates interest in "whole-body" assessment of HER2 status using molecular imaging. We evaluated the role of HER2-targeted molecular imaging in detecting HER2-positive BC lesions and patients unlikely to respond to T-DM1. Patients underwent zirconium-89 (89Zr) trastuzumab (HER2) PET/CT and [18F]-2-fluoro-2-deoxy-D-glucose (FDG) PET/CT before T-DM1 initiation. Based on 89Zr-trastuzumab uptake, lesions were visually classified as HER2-positive (visible/high uptake) or HER2-negative (background/close to background activity). According to proportion of FDG-avid tumor load showing 89Zr-trastuzumab uptake (entire/dominant part or minor/no part), patients were classified as HER2-positive and HER2-negative, respectively. Out of 265 measurable lesions, 93 (35%) were HER2-negative, distributed among 42 of the 90 included patients. Of these, 18 (19%) lesions belonging to 11 patients responded anatomically (>30% decrease in axial diameter from baseline) after three T-DM1 cycles, resulting in an 81% negative predictive value (NPV) of the HER2 PET/CT. In combination with early metabolic response assessment on FDG PET/CT performed before the second T-DM1 cycle, NPVs of 91% and 100% were reached in predicting lesion-based and patient-based (RECIST1.1) response, respectively. Therefore, HER2 PET/CT, alone or in combination with early FDG PET/CT, can successfully identify BC lesions and patients with a low probability of clinical benefit from T-DM1.

Surgery of the primary tumor in patients with de novo metastatic breast cancer: a nationwide population-based retrospective cohort study in Belgium.

PURPOSE: We aimed to assess the impact of surgery of primary tumor in overall survival (OS) of women with de novo metastatic breast cancer. METHODS: Nationwide, population-based retrospective cohort study of women diagnosed with de novo metastatic breast cancer in Belgium, between Jan/2010-Dec/2014. Data was obtained from the Belgian Cancer Registry and administrative databases. "Surgery" group was defined by surgery of primary tumor up to nine months after diagnosis. We excluded women who did not receive systemic treatment or did not complete nine months follow-up after diagnosis. All the subsequent analyses reporting on overall survival and the stratified outcome analyses were performed based on this nine-month landmark cohort. OS was estimated using Kaplan-Meier method and compared using adjusted Cox proportional hazards models controlling for confounders with 95% confidence intervals (CI). We performed a stratified analysis according to surgery timing and a propensity score matching analysis. RESULTS: 1985 patients, 534 (26.9%) in the "Surgery" and 1451 (73.1%) in the "No Surgery" group. Patients undergoing surgery were younger (p < 0.001), had better performance status (PS) (p < 0.001), and higher proportion of HER2-positive and triple-negative breast cancer (p = 0.012). Median follow-up was 86.0 months (82.6-88.5). Median OS was 60.1 months (57.1-68.2) in the "Surgery" vs. 41.9 months (39.8-44.2) in the "No Surgery" group (adjusted HR 0.56; 0.49-0.64). OS was similar when surgery was performed upfront or after systemic treatment. Propensity score matching analysis confirmed the same findings. CONCLUSION: Among patients receiving systemic treatment for de novo metastatic breast cancer and surviving nine months or more, those who received surgery of the primary tumor within nine months of diagnosis have longer subsequent survival than those who did not.

The impact of erythropoiesis-stimulating agents administration concomitantly with adjuvant anti-HER2 treatments on the outcomes of patients with early breast cancer: a sub-analysis of the ALTTO study.

PURPOSE: To assess whether erythropoiesis-stimulating agents (ESA) administration impacts the outcomes of patients with HER2-positive early breast cancer (EBC). METHODS: ALTTO (NCT00490139) patients were categorized by ESA use during adjuvant anti-HER2 treatment. Disease-free-survival (DFS), overall survival (OS), and time-to-distant recurrence (TTDR) were analyzed by ESA administration, with subgroup analyses according to prognostic factors. Log-rank tests and Cox modeling were performed. Adverse events (AEs) of ESA-interest were compared. RESULTS: Among 8381 patients recruited in ALTTO, 123 (1.5%) received ESA concomitantly with study treatment. The median age of patients receiving ESA was 54 years, 39.0% premenopausal, most had tumor size > 2 cm (56.9%), node-positive (58.5%), and positive estrogen receptor expression (61.8%). Median follow-up was shorter in the ESA group [6.1 years (IQR 5.3-7.0) vs. 6.9 years (6.0-7.1); p < 0.001]. There was no DFS difference by ESA administration (log-rank p = 0.70), with 3- and 7-year DFS of 89.2% (95% CI 81.8-93.8%) and 81.6% (71.4-88.5%) in ESA group vs. 88.3% (87.6-89.0%) and 80.0% (79.1-80.9%) in No-ESA group. In subgroup analyses, the interaction of ESA administration with menopausal status was statistically significant (unadjusted p = 0.024; stratified p = 0.033), favoring premenopausal women receiving ESA. We observed no significant association of ESA administration with OS (log-rank p = 0.57; 7-year OS in ESA 88.6% vs. 90.0% in non-ESA) or TTDR. ESA-interest AEs were experienced by eight (6.5%) patients receiving ESA and 417 (5.1%) in the No-ESA group (p = 0.41). CONCLUSION: ESA administration to patients receiving adjuvant anti-HER2 treatment for HER2-positive EBC was safe and not associated with a negative impact on survival outcomes.

First-in-human study of SBRT and adenosine pathway blockade to potentiate the benefit of immunochemotherapy in early-stage luminal B breast cancer: results of the safety run-in phase of the Neo-CheckRay trial.

BACKGROUND: Luminal B breast cancer (BC) presents a worse prognosis when compared with luminal A BC and exhibits a lower sensitivity to chemotherapy and a lower immunogenicity in contrast to non-luminal BC subtypes. The Neo-CheckRay clinical trial investigates the use of stereotactic body radiation therapy (SBRT) directed to the primary tumor in combination with the adenosine pathway inhibitor oleclumab to improve the response to neo-adjuvant immuno-chemotherapy in luminal B BC. The trial consists of a safety run-in followed by a randomized phase II trial. Here, we present the results of the first-in-human safety run-in. METHODS: The safety run-in was an open-label, single-arm trial in which six patients with early-stage luminal B BC received the following neo-adjuvant regimen: paclitaxel q1w×12 → doxorubicin/cyclophosphamide q2w×4; durvalumab (anti-programmed cell death receptor ligand 1 (PD-L1)) q4w×5; oleclumab (anti-CD73) q2w×4 → q4w×3 and 3×8 Gy SBRT to the primary tumor at week 5. Surgery must be performed 2-6 weeks after primary systemic treatment and adjuvant therapy was given per local guidelines, RT boost to the tumor bed was not allowed. Key inclusion criteria were: luminal BC, Ki67≥15% or histological grade 3, MammaPrint high risk, tumor size≥1.5 cm. Primary tumor tissue samples were collected at three timepoints: baseline, 1 week after SBRT and at surgery. Tumor-infiltrating lymphocytes, PD-L1 and CD73 were evaluated at each timepoint, and residual cancer burden (RCB) was calculated at surgery. RESULTS: Six patients were included between November 2019 and March 2020. Median age was 53 years, range 37-69. All patients received SBRT and underwent surgery 2-4 weeks after the last treatment. After a median follow-up time of 2 years after surgery, one grade 3 adverse event (AE) was reported: pericarditis with rapid resolution under corticosteroids. No grade 4-5 AE were documented. Overall cosmetical breast evaluation after surgery was 'excellent' in four patients and 'good' in two patients. RCB results were 2/6 RCB 0; 2/6 RCB 1; 1/6 RCB 2 and 1/6 RCB 3. CONCLUSIONS: This novel treatment combination was considered safe and is worth further investigation in a randomized phase II trial. TRIAL REGISTRATION NUMBER: NCT03875573.

Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial.

Chemo-immunotherapy is the first-line standard of care for patients with PD-L1 positive metastatic triple-negative breast cancer (mTNBC). SYNERGY (NCT03616886) is a dose-finding phase I and a randomized phase II, open-label trial evaluating if targeting the immunosuppressive adenosine pathway can enhance the antitumor activity of chemo-immunotherapy. The phase I part included 6 patients with untreated locally-advanced or mTNBC to determine the safety and recommended phase II dose of the anti-CD73 antibody oleclumab in combination with the anti-PD-L1 durvalumab and 12 cycles of weekly carboplatin and paclitaxel. In the phase II part, 127 women were randomized 1:1 to receive chemo-immunotherapy, with (arm A) or without (arm B) oleclumab. The primary endpoint was the clinical benefit rate at week 24, defined as stable disease, partial or complete response per RECIST v1.1. Secondary endpoints included objective response rate, duration of response, survival outcomes (progression-free survival and overall survival), and safety. The trial did not meet its primary endpoint, as the 24-week clinical benefit rate was not significantly improved by adding oleclumab (43% vs. 44%, p = 0.61). Exploratory median progression-free survival was 5.9 months in arm A as compared to 7.0 months in arm B (p = 0.90). The safety profile was manageable in both arms.

Optimizing treatment for HER2-positive HR-positive breast cancer.

Triple-positive breast tumors overexpress human epidermal growth factor receptor 2 (HER2) and are positive for hormone receptor (HR) expression. Data from real-life and clinical trials show that estrogen receptor (ER) expression affects the response to combinations of anti-HER2 and associated systemic therapies. Despite triple-positive tumors having decreased response rates compared to HR-negative/HER2-positive breast cancers, optimizing anti-HER2 treatment with dual anti-HER2 blockade remains important for optimal disease control. Preclinical data on the cross-talk between ER and growth factor receptor pathways show the efficacy of combinations of endocrine therapy and anti-HER2 drugs, which is confirmed in the clinic. Molecular dissection of triple-positive breast cancer might provide the rational for additional therapeutic strategies and the identification of promising biomarkers. This review summarizes data on systemic treatment efficacy from major clinical trials and perspectives for future clinical research in triple-positive breast cancer.

Immunotherapy in breast cancer: an overview of current strategies and perspectives.

Recent progress in immunobiology has led the way to successful host immunity enhancement against breast cancer. In triple-negative breast cancer, the combination of cancer immunotherapy based on PD-1/PD-L1 immune checkpoint inhibitors with chemotherapy was effective both in advanced and early setting phase 3 clinical trials. These encouraging results lead to the first approvals of immune checkpoint inhibitors in triple-negative breast cancer and thus offer new therapeutic possibilities in aggressive tumors and hard-to-treat populations. Furthermore, several ongoing trials are investigating combining immunotherapies involving immune checkpoint inhibitors with conventional therapies and as well as with other immunotherapeutic strategies such as cancer vaccines, CAR-T cells, bispecific antibodies, and oncolytic viruses in all breast cancer subtypes. This review provides an overview of immunotherapies currently under clinical development and updated key results from clinical trials. Finally, we discuss the challenges to the successful implementation of immune treatment in managing breast cancer and their implications for the design of future clinical trials.

Six-year absolute invasive disease-free survival benefit of adding adjuvant pertuzumab to trastuzumab and chemotherapy for patients with early HER2-positive breast cancer: A Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of the APHINITY (BIG 4-11) trial.

AIM: The APHINITY trial showed that adding adjuvant pertuzumab (P) to trastuzumab and chemotherapy, compared with adding placebo (Pla), significantly improved invasive disease-free survival (IDFS) for patients with HER2+ early breast cancer both overall and for the node-positive (N+) cohort. We explored whether adding P could benefit some N- subpopulations and whether to consider de-escalation for some N+ subpopulations. METHODS: Subpopulation Treatment Effect Pattern Plot (STEPP) is an exploratory, graphical method that plots estimates of treatment effect for overlapping patient subpopulations defined by a covariate of interest. We used STEPP to estimate Kaplan-Meier differences in 6-year IDFS percentages (P minus Pla: Δ ± standard error [SE]), both overall and by nodal status, for overlapping subpopulations defined by (1) a clinical composite risk score, (2) tumour infiltrating lymphocytes (TILs) percentage, and (3) human epidermal growth factor receptor 2 (HER2) FISH copy number. Because of multiplicity, a Δ of at least three SE is required to warrant attention. RESULTS: The average absolute gains in 6-year IDFS percentages were 2.8 ± 0.9 overall; 4.5 ± 1.2 for N+ and 0.1 ± 1.1 for N-. Largest gains were for patients with intermediate clinical composite risk (5.3 ± 1.9 overall; 6.9 ± 2.3 N+; 4.0 ± 3.0 N-), highest TILs percentage (6.3 ± 1.7 overall; 7.4 ± 2.4 N+; 3.2 ± 1.7 N-), and intermediate HER2 copy number (2.8 ± 1.9 overall; 7.4 ± 2.5 N+; -1.3 ± 1.9 N-), but clear evidence indicating a pattern of differential subpopulation treatment effects was lacking. CONCLUSIONS: STEPP plots for N- did not identify subpopulations clearly benefiting from adding P, and those for N+ did not identify subpopulations warranting de-escalation. TILs percentage appeared to be more predictive of P treatment effect than clinical composite risk score. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT01358877.

FDG positron emission tomography imaging and ctDNA detection as an early dynamic biomarker of everolimus efficacy in advanced luminal breast cancer.

Biomarkers to identify patients without benefit from adding everolimus to endocrine treatment in metastatic breast cancer (MBC) are needed. We report the results of the Pearl trial conducted in five Belgian centers assessing 18F-FDG-PET/CT non-response (n = 45) and ctDNA detection (n = 46) after 14 days of exemestane-everolimus (EXE-EVE) to identify MBC patients who will not benefit. The metabolic non-response rate was 66.6%. Median PFS in non-responding patients (using as cut-off 25% for SUVmax decrease) was 3.1 months compared to 6.0 months in those showing response (HR: 0.77, 95% CI: 0.40-1.50, p = 0.44). The difference was significant when using a "post-hoc" cut-off of 15% (PFS 2.2 months vs 6.4 months). ctDNA detection at D14 was associated with PFS: 2.1 months vs 5.0 months (HR-2.5, 95% CI: 1.3-5.0, p = 0.012). Detection of ctDNA and/or the absence of 18F-FDG-PET/CT response after 14 days of EXE-EVE identifies patients with a low probability of benefiting from treatment. Independent validation is needed.

Overcoming Barriers to Clinical Trials Cooperation: The Breast International Group Example.

Clinical trials cooperation is not a luxury; it is a necessity, now more than ever, first in light of the segmentation of tumors according to their molecular targets-which are being matched to an increasing number of competitive drugs-and second because it is the only chance to maintain academic research centered on addressing patients' needs. In its 21 years of existence, the Breast International Group, an umbrella organization supporting the activities of 54 member groups across six continents, has been confronted with challenges that include (1) keeping trust and motivation within the network; (2) improving the interface between academia and industry; (3) improving patient involvement and trust in clinical trials; and (4) fundraising for noncommercial research. We describe how these challenges have been addressed so far, with the hope of empowering the next generation of clinical investigators.

CDK4/6 and PI3K inhibitors: A new promise for patients with HER2-positive breast cancer.

BACKGROUND: HER2-positive (HER2+) breast cancer represents a heterogeneous breast cancer subtype, including both oestrogen receptor (ER) positive and negative tumours. A deeper understanding of the crosstalk between ER and HER2 receptor pathways has led to the development of treatment strategies consisting of a simultaneous blockade of both signalling pathways, as a reasonable approach to prevent the onset of mechanisms of resistance. METHODS: This review was based on the material searched on PubMed, MEDLINE and Embase databases and on conference proceedings from major oncology conferences up to 15 December 2020. The search strategy included the following keywords: 'HER2-positive breast cancer', 'CDK4-6 inhibitors' and 'PI3K inhibitors', and was adapted for use with different bibliographic databases. RESULTS: CDK4/6 and PI3K inhibitors are two classes of agents already approved in patients with hormone receptor positive, HER2-negative breast cancer. Recently, promising data with their use have been also shown in HER2+ disease. Results from preclinical and clinical studies are shedding light on the role of these classes of agents in HER2+ breast cancer, and are paving the road for a forthcoming change in clinical practice. CONCLUSIONS: Treatment landscape for HER2+ breast cancer is rapidly changing, and CDK4/6 and PI3K inhibitors represent a new promising strategy to improve patients' outcomes.

Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D).

AIM: To present the pre-specified analyses of >5-years follow-up of the Phase III ALTTO trial. PATIENTS AND METHODS: 8381 patients with stage I-III HER2 positive breast cancer randomised to chemotherapy plus 1-year of trastuzumab (T), oral lapatinib (L; no longer evaluated), trastuzumab followed by lapatinib (T→L), and lapatinib + trastuzumab (L+T). The primary endpoint was disease-free survival (DFS). A secondary analysis examined DFS treatment effects by hormone receptor status, nodal status and chemotherapy timing; time to recurrence; overall survival (OS) and safety (overall and cardiac). RESULTS: At a median follow-up of 6.9 years, 705 DFS events for L+T versus T were observed. Hazard Ratio (HR) for DFS was 0.86 (95% CI, 0.74-1.00) for L+T versus T and 0.93 (95% CI, 0.81-1.08) for T→L versus T. The 6-year DFS were 85%, 84%, and 82% for L+T, T→L, and T, respectively. HR for OS was 0.86 (95% CI, 0.70-1.06) for L+T versus T and 0.88 (95% CI, 0.71-1.08) for T→L versus T. The 6-year OS were 93%, 92%, and 91% for L+T, T→L, and T, respectively. Subset analyses showed a numerically better HR for DFS in favour of L+T versus T for the hormone-receptor-negative [HR 0.80 (95% CI, 0.64-1.00; 6-yr DFS% = 84% versus 80%)] and the sequential chemotherapy [HR 0.83 (95% CI, 0.69-1.00; 6-yr DFS% = 83% versus79%)] subgroups. CONCLUSION: T+L did not significantly improve DFS and OS over T alone, both with chemotherapy, and, therefore, cannot be recommended for adjuvant treatment of early-stage HER2-positive breast cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00490139.

Cardiotoxicity of immune checkpoint inhibitors: A systematic review and meta-analysis of randomised clinical trials.

BACKGROUND: Immune checkpoint inhibitors (ICIs) may cause potentially life-threatening adverse events (AEs), but the risk of cardiotoxicity has not been fully investigated. It is also unknown whether ICI combinations increase cardiotoxicity compared with single ICI. We aimed to assess the cardiotoxicity of ICI in a range of tumour types. METHODS: This systematic review and meta-analysis was conducted according to PRISMA guidelines (PROSPERO registration number: CRD42020183524). A systematic search of PubMed, MEDLINE, Embase databases, and conference proceedings was performed up to 30 June 2020. All randomised clinical trials comparing ICI with other treatments (primary objective) or dual-agent ICI versus single-agent ICI (secondary objective) in any solid tumour were included. Pooled risk ratios (RRs) with 95% confidence intervals (95% CIs) for cardiotoxicity events were calculated using random effect models. RESULTS: Eighty studies including 35,337 patients were included in the analysis (66 studies with 34,664 patients for the primary endpoint and 14 studies with 673 patients for the secondary endpoint). No significant differences in terms of cardiac AEs were observed between ICI and non-ICI groups (RR 1.14, 95% CI 0.88-1.48, p = 0.326) nor between dual ICI and single ICI groups (RR 1.91, 95% CI 0.52-7.01, p = 0.329). Myocarditis incidence did not significantly differ between ICI and non-ICI groups (RR 1.11, 95% CI 0.64-1.92, p = 0.701) nor between dual ICI and single ICI groups (RR 1.10, 95% CI 0.31-3.87, p = 0.881). No differences were observed in subgroup analyses according to tumour type, setting of disease, treatment line, and type of treatment. CONCLUSION: The use of ICI as single or combination regimens is not associated with increased risk of cardiotoxicity.

Impact of HIV infection on baseline characteristics and survival of women with breast cancer.

BACKGROUND: As women living with HIV (WLWH) become older, their risk of developing breast cancer increases. Nonetheless, literature is conflicting regarding tumor stage, distribution of subtypes and overall survival among WLWH vs. HIV-negative women with breast cancer. We assessed differences in clinicopathological characteristics and overall survival between these two groups. METHODS: Systematic review and meta-analysis using MEDLINE, Scopus, ISI Web of Knowledge, LILACS, SciELO and conference abstracts up to 1 January 2020. Cross-sectional/cohort studies comparing baseline characteristics (stage and/or subtypes) and/or overall survival of WLWH vs. HIV-negative women with breast cancer were included. We performed random-effects meta-analyses to estimate summary statistics and subgroup analyses according to region of the world. RESULTS: Eighteen studies [4 from North America, 14 from sub-Saharan Africa (SSA)] were included, with 3174 WLWH and 2 394 598 HIV-negative women. WLWH from North America and SSA were more likely to present with stage III/IV disease compared with HIV-negative women - pooled odds ratio (pOR) 1.76 [95% confidence interval (CI):1.58-1.95] and pOR 1.23 (95% CI: 1.06-1.42), respectively. WLWH from SSA were also less likely to have estrogen receptor-positive/HER2-negative tumors (pOR 0.81; 95% CI: 0.66-0.99). After adjustment, WLWH had worse overall survival compared with HIV-negative women, both in North America [pooled adjusted hazard ratio (aHR) 2.45; 95% CI: 1.11-5.41] and SSA (aHR 1.43; 95% CI: 1.06-1.92). CONCLUSION: Compared with HIV-negative women, WLWH are diagnosed with breast cancer at a more advanced stage and have a worse overall survival. These results should raise awareness regarding the detection and survival gap among WLWH with breast cancer and further studies are needed to decipher the reasons behind these disparities.

Survival Impact and Cost-Effectiveness of a Multidisciplinary Tumor Board for Breast Cancer in Mozambique, Sub-Saharan Africa.

BACKGROUND: Despite the international endorsement of multidisciplinary tumor boards (MTBs) for breast cancer care, implementation is suboptimal worldwide, and evidence regarding their effectiveness in developing countries is lacking. We assessed the impact on survival and the cost-effectiveness of implementing an MTB in Mozambique, sub-Saharan Africa. MATERIALS AND METHODS: This prospective cohort study included 205 patients with breast cancer diagnosed between January 2015 and August 2017 (98 before and 107 after MTB implementation), followed to November 2019. Pre- and post-MTB implementation subcohorts were compared for clinical characteristics, treatments, and overall survival. We used hazard ratios and 95% confidence intervals (CI), computed by Cox proportional hazards regression. The impact of MTB implementation on the cost per quality-adjusted life year (QALY) was estimated from the provider perspective. RESULTS: We found no significant differences between pre- and post-MTB subcohorts regarding clinical characteristics or treatments received. Among patients with early breast cancer (stage 0-III; n = 163), the 3-year overall survival was 48.0% (95% CI, 35.9-59.1) in the pre-MTB and 73.0% (95% CI, 61.3-81.6) in the post-MTB subcohort; adjusted hazard ratio, 0.47 (95% CI, 0.27-0.81). The absolute 3-year mean cost increase was $119.83 per patient, and the incremental cost-effectiveness ratio was $802.96 per QALY, corresponding to 1.6 times the gross domestic product of Mozambique. CONCLUSION: The implementation of a MTB in Mozambique led to a 53% mortality decrease among patients with early breast cancer, and it was cost-effective. These findings highlight the feasibility of implementing this strategy and the need for scaling-up MTBs in developing countries, as a way to improve patient outcomes. IMPLICATIONS FOR PRACTICE: Currently, more than half of the deaths from breast cancer in the world occur in developing countries. Strategies that optimize care and that are adjusted for available resources are needed to improve the outcomes of patients with breast cancer in these regions. The discussion of cases at multidisciplinary tumor boards (MTBs) may improve survival outcomes, but implementation is suboptimal worldwide, and evidence regarding their effectiveness in developing countries is lacking. This study evaluated the impact of implementing an MTB on the care and survival of patients with breast cancer in Mozambique, sub-Saharan Africa and its cost-effectiveness in this low-income setting.