An effort to improve the collection of patient-generated data: readability and understandability of patient-reported outcomes measures in a survivorship cohort.

PURPOSE: In this study, we evaluated readability and understandability of nine French-language Patient-Reported Outcome Measures (PROMs) that are currently used in a contemporary longitudinal cohort of breast cancer survivors as part of an effort to improve equity in cancer care and research. METHODS: Readability of PROMs was assessed using the Flesh Reading Ease Score (FRES), the Gunning's Fog Index (FOG), and the FRY graphics. Readability was considered ideal if mean score ≤ 6th-grade level and acceptable if between 6th and 8th grade. Understandability was evaluated using the Patient Education Materials Assessment Tool and defined as ideal if PEMAT ≥ 80%. The Evaluative Linguistic Framework for Questionnaires (ELF-Q) provided additional qualitative elements to assess understandability. Plain-language best practice was met if both readability and understandability were ideal. RESULTS: None of the 9 PROMs evaluated had ideal readability scores and only 1 had an acceptable score. Understandability ranged from 55% to 91%, and only 3 PROMs had ideal scores. ELF-Q identified points for improvement in several understandability dimensions of the PROMs. None of the instruments met the definition of plain-language best practice. CONCLUSION: None of the studied PROMs met the standards of readability and understandability. Future development and translation of PROMs should follow comprehensive linguistic and cultural frameworks to ensure plain-language standards and enhance equitable patient-centered care and research.

Patient-Reported Quality of Life 6 Years After Breast Cancer.

This cohort study assesses quality-of-life trajectories up to 6 years after breast cancer diagnosis among individuals in France.

Chemotherapy-Related Amenorrhea and Quality of Life Among Premenopausal Women With Breast Cancer.

Importance: Younger survivors of breast cancer frequently report more treatment-related symptoms, mostly related to the menopausal transition. Objective: To assess factors associated with chemotherapy-related amenorrhea (CRA) and to evaluate its association with long-term quality of life (QOL). Design, Setting, and Participants: The prospective, longitudinal Cancer Toxicities Study, a multicenter French cohort study, includes women with a diagnosis of stage I to III breast cancer and collects data approximately yearly after diagnosis. The current study reports outcomes up to 4 years after diagnosis for participants enrolled from 2012 to 2017. Participants included premenopausal women younger than 50 years treated with chemotherapy and not receiving adjuvant ovarian function suppression. Data analysis was performed from September 2021 to June 2023. Exposures: Clinical, socioeconomic, tumor, and treatment characteristics assessed at diagnosis (for the analysis of factors associated with CRA) and persistent CRA (for the QOL analysis). Main Outcomes and Measures: The main outcome of interest was CRA at year 1 (Y1), year 2 (Y2), and year 4 (Y4) after diagnosis. Generalized estimating equations assessed associations of exposure variables with CRA. In the QOL analysis, QOL at Y4 (assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 and BR23) was the outcome of interest. Multivariable random-effect mixed models assessed the association of persistent CRA (ie, never recovering menses after treatment) with QOL. Results: Among 1636 women, the mean (SD) age at diagnosis was 42.2 (5.6) years. Overall, 1242 of 1497 women (83.0%) reported CRA at Y1, 959 of 1323 women (72.5%) reported it at Y2, and 599 of 906 women (66.1%) reported it at Y4. Older age vs 18 to 34 years (adjusted odds ratio [OR] for 35 to 39 years, 1.84 [95% CI, 1.32 to 2.56]; adjusted OR for 40 to 44 years, 5.90 [95% CI, 4.23 to 8.24]; and adjusted OR for ≥45 years, 21.29 [95% CI, 14.34 to 31.61]) and receipt of adjuvant tamoxifen (adjusted OR, 1.97 [95% CI, 1.53 to 2.53]) were associated with higher likelihood of CRA. In the QOL analysis, 416 of 729 women (57.1%) had persistent CRA. However, late menses recovery among women aged 18 to 34 years with no menses at Y2 were reported by 11 of 21 women (52.4%) between Y2 and Y4. Persistent CRA was associated with worse insomnia (mean difference vs recovery at any time, 9.9 points [95% CI, 3.2 to 16.5 points]; P = .004), systemic therapy-related adverse effects (mean difference, 3.0 points [95% CI, 0.2 to 5.8 points]; P = .04), and sexual functioning (mean difference, -9.2 points [95% CI, -14.3 to -4.1 points]; P < .001) at Y4. Conclusions and Relevance: In this cohort study of premenopausal women with breast cancer, persistent CRA was common, although some women recovered menses late, and was associated with worse long-term QOL. This study can help inform risk communication, personalized counseling, and early supportive care referrals for such patients.

Implementing a PROACTive Care Pathway to Empower and Support Survivors of Breast Cancer.

PURPOSE: Optimal comprehensive survivorship care is insufficiently delivered. To increase patient empowerment and maximize the uptake of multidisciplinary supportive care strategies to serve all survivorship needs, we implemented a proactive survivorship care pathway for patients with early breast cancer at the end of primary treatment phase. METHODS: Pathway components included (1) a personalized survivorship care plan (SCP), (2) face-to-face survivorship education seminars and personalized consultation for supportive care referrals (Transition Day), (3) a mobile app delivering personalized education and self-management advice, and (4) decision aids for physicians focused on supportive care needs. A mixed-methods process evaluation was performed according to the Reach, Effectiveness, Adoption, Implementation and Maintenance framework including administrative data review, pathway experience survey (patient, physician, and organization), and focus group. The primary objective was patient-perceived satisfaction with the pathway (predefined progression criteria for pathway continuation ≥70%). RESULTS: Over 6 months, 321 patients were eligible for the pathway and received a SCP and 98 (30%) attended the Transition Day. Among 126 patients surveyed, 77 (66.1%) responded. 70.1% received the SCP, 51.9% attended the Transition Day, and 59.7% accessed the mobile app. 96.1% of patients were very or completely satisfied with the overall pathway, whereas perceived usefulness was 64.8% for the SCP, 90% for the Transition Day, and 65.2% for the mobile app. Pathway implementation seemed to be positively experienced by physicians and the organization. CONCLUSION: Patients were satisfied with a proactive survivorship care pathway, and the majority reported that its components were useful in supporting their needs. This study can inform the implementation of survivorship care pathways in other centers.

Impact of Anti-HER2 Therapy Alone and With Weekly Paclitaxel on the Ovarian Reserve of Young Women With HER2-Positive Breast Cancer.

BACKGROUND: The potential gonadotoxicity of anti-HER2 agents remains largely unknown, and limited, conflicting evidence exists for taxanes. Antimüllerian hormone (AMH) is an established biomarker of ovarian reserve that may aid in quantifying anticancer treatment-induced gonadotoxicity. PATIENTS AND METHODS: The present biomarker analysis of the randomized phase III neoadjuvant NeoALTTO trial included premenopausal women aged ≤45 years at diagnosis of HER2-positive early breast cancer with available frozen serum samples at baseline (ie, before anticancer treatments), at week 2 (ie, the "biological window" of anti-HER2 therapy alone), and/or at the time of surgery (ie, after completing paclitaxel + anti-HER2 therapy, before starting adjuvant chemotherapy). RESULTS: The present analysis included 130 patients with a median age of 38 years (interquartile ratio [IQR], age 33-42 years). AMH values at the 3 time points differed significantly (P<.001). At baseline, median AMH levels were 1.29 ng/mL (IQR, 0.56-2.62 ng/mL). At week 2, a small but significant reduction in AMH levels was observed (median, 1.10 ng/mL; IQR, 0.45-2.09 ng/mL; P<.001). At surgery, a larger significant decline in AMH levels was observed (median, 0.01 ng/mL; IQR, 0.01-0.03 ng/mL; P<.001). Although the type of anti-HER2 treatment (trastuzumab and/or lapatinib) did not seem to impact the results, age and pretreatment ovarian reserve had a major influence on treatment-induced gonadotoxicity risk. CONCLUSIONS: This NeoALTTO biomarker analysis showed that anti-HER2 therapies alone had limited gonadotoxicity but that the addition of weekly paclitaxel resulted in marked AMH decline with possible negative implications for subsequent ovarian function and fertility.

Facing points of view: Representations on adjuvant endocrine therapy of premenopausal patients after breast cancer and their healthcare providers in France. The FOR-AD study.

PURPOSE: Adjuvant endocrine therapy (ET) for 5-10 years is the backbone of the therapeutic strategy in patients with hormone receptor positive (HR+) early breast cancer (BC). However, long-term adherence to adjuvant ET represents a major challenge for most patients. According to prior studies, side effects of adjuvant ET are an important reason for poor adherence. In contrast, better communication and relational bond between patients and healthcare providers (HCPs) may improve adherence. The FOR-AD (Focus on non-adherence) study aimed at better understanding the representation of adjuvant ET by patients and their HCPs, in order to improve the care process. METHODS: Three focus groups of premenopausal women (receiving adjuvant ET for variable amount of time) and two focus groups of HCPs (including oncologists, pharmacists, and nurses) were conducted, each including around ten participants. Thematic analyses using a general inductive approach were constructed to report participants' representations. RESULTS: Two main themes emerged across groups, and appeared of major importance. Representations on adjuvant ET were often homogenous within each group, but differed between patients and their HCPs. The relationship between both groups was considerably discussed, particularly its importance in facilitating adherence to adjuvant ET. Suggestions on improving the care process were also given, such as systematically including psychologists in follow-up care paths and having a nurse navigator follow patients under treatment with adjuvant ET. CONCLUSION: The present qualitative exploration may help buildi future tailored interventions to improve adherence to adjuvant ET, in particular regarding the role of nurse navigators.

Contraceptive Use in Premenopausal Women With Early Breast Cancer.

Importance: As life span has increased among patients with cancer, survivorship has become an important component of breast cancer care. Among survivorship concerns, adequate contraceptive counseling is needed for premenopausal patients who are not seeking to become pregnant. Objective: To examine contraceptive use and chosen methods and to assess factors associated with contraceptive use over time in patients with early breast cancer. Design, Setting, and Participants: The Cancer Toxicity (CANTO) study was a multicenter nationwide prospective cohort study that enrolled women diagnosed with stage I to stage III breast cancer in France between March 2012 and December 2017. This analysis included 2900 premenopausal women who were 50 years of age or younger at diagnosis. Data were analyzed from July 2020 to July 2022. Exposures: Contraceptive use and method at diagnosis, shortly after the end of primary treatment (year 1), and during follow-up (year 2). Main Outcomes and Measures: Contraceptive use and methods were longitudinally evaluated at diagnosis, year 1, and year 2 after breast cancer diagnosis. Multivariable logistic regression models were used to assess the associations of clinical, socioeconomic, treatment, adverse effect, and patient-reported outcome variables with contraceptive use after diagnosis. Results: A total of 2900 patients (mean [SD] age, 43.1 [5.6] years) were included in the analysis; 2050 of 2894 women (70.8%) received chemotherapy, and 2305 of 2880 women (80.0%) received endocrine therapy. After diagnosis, 1182 of 2625 patients (45.0%) at year 1 and 1553 of 2363 patients (65.7%) at year 2 reported consulting with a gynecologist in the previous year. At diagnosis, 1487 of 2744 patients (54.2%) reported contraceptive use, with most patients (921 of 1470 women [62.7%]) using hormonal methods. The use of contraception significantly decreased after diagnosis (911 of 2342 patients [38.9%] at year 1 and 808 of 1961 patients [41.2%] at year 2; P < .001 for trend), when most patients (848 of 900 women [94.2%] at year 1 and 767 of 805 women [95.3%] at year 2) reported use of nonhormonal methods; these methods were primarily reversible mechanical approaches (copper intrauterine devices: 656 of 848 patients [77.4%] at year 1 and 577 of 767 patients [75.2%] at year 2; male condoms: 115 of 848 patients [13.6%] at year 1 and 110 of 767 patients [14.3%] at year 2). In the multivariable model, factors significantly associated with contraceptive use at year 1 included using contraception at diagnosis (adjusted odds ratio [aOR], 4.02; 95% CI, 3.15-5.14), being younger (aOR, 1.09; 95% CI, 1.07-1.13 per decreasing year), having better sexual function (aOR, 1.13; 95% CI, 1.07-1.19 per 10-point increment), having children (aOR, 4.21; 95% CI, 1.80-9.86), reporting the presence of leukorrhea (aOR, 1.32; 95% CI, 1.03-1.70), receiving tamoxifen treatment alone (aOR, 1.39; 95% CI, 1.01-1.92), and consulting with a gynecologist in the previous year (aOR, 1.29; 95% CI, 1.02-1.63). Similar factors were associated with contraceptive use at year 2, with the addition of partnered status (aOR, 1.61; 95% CI, 1.07-2.44). Conclusions and Relevance: Findings from this study support the importance of raising awareness and improving targeted contraceptive counseling for premenopausal women with early breast cancer.

Timelines to initiate a phase III trial across the globe: a sub-analysis of the APHINITY trial.

Background: Geographic location and national income may influence access to innovation in healthcare. We aimed to study if geographical location and national income influenced the timelines to activate the global phase III APHINITY trial, evaluating adjuvant pertuzumab in patients with HER2-positive early breast cancer. Methods: Time from regulatory authority (RA) submission to approval (RAA), time to Ethics Committee/Institutional Review Board (EC/IRB) approval, time from study approval by EC/IRB to first randomised patient and from first to last randomised patient were collected. Analyses were conducted grouping countries by geographical region or economic income classification. Results: Forty-one countries (of 42) had data available regarding all relevant timelines. No statistical difference was observed between the time to RAA and geographical region (p = 0.47), although there was a trend to longer time to RAA in upper middle-income economies (p = 0.07). Except for time from first to last patient randomised, there was wide variation in timelines overall and within geographical regions and economic income groups. Conclusions: Geographical location and income classification did not appear to be the major drivers influencing time for clinical trial activation. Wide variability in activation timelines within geographical regions and income groups exists and is worthy of further investigation.

Management of Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases: ASCO Guideline Update.

PURPOSE: To provide updated evidence- and consensus-based guideline recommendations to practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer up to 2021. METHODS: An Expert Panel conducted a targeted systematic literature review (for both systemic therapy for non-CNS metastases and for CNS metastases of HER2+ guideline updates) that identified 545 articles. Outcomes of interest included overall survival, progression-free survival, and adverse events. RESULTS: Of the 545 publications identified and reviewed, six on systemic therapy were identified to form the evidentiary basis for the systemic therapy for CNS metastases guideline recommendations. RECOMMENDATIONS: Patients with brain metastases should receive appropriate local therapy and systemic therapy, if indicated. Local therapies include surgery, whole-brain radiotherapy, and stereotactic radiosurgery. Memantine and hippocampal avoidance should be added to whole-brain radiotherapy when possible. Treatments depend on factors such as patient prognosis, presence of symptoms, resectability, number and size of metastases, prior therapy, and whether metastases are diffuse. Other options include systemic therapy, best supportive care, enrollment onto a clinical trial, and/or palliative care. There are insufficient data to recommend for or against performing routine magnetic resonance imaging to screen for brain metastases; clinicians should have a low threshold for magnetic resonance imaging of the brain because of the high incidence of brain metastases among patients with HER2-positive advanced breast cancer.Additional information is available at www.asco.org/breast-cancer-guidelines.

Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: ASCO Guideline Update.

PURPOSE: To update evidence-based guideline recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. METHODS: An Expert Panel conducted a targeted systematic literature review (for both systemic treatment and CNS metastases) and identified 545 articles. Outcomes of interest included efficacy and safety. RESULTS: Of the 545 publications identified and reviewed, 14 were identified to form the evidentiary basis for the guideline recommendations. RECOMMENDATIONS: HER2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane for first-line treatment and trastuzumab deruxtecan for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations. There is a lack of head-to-head trials; therefore, there is insufficient evidence to recommend one regimen over another. The patient and the clinician should discuss differences in treatment schedule, route, toxicities, etc during the decision-making process. Options include regimens with tucatinib, trastuzumab emtansine, trastuzumab deruxtecan (if either not previously administered), neratinib, lapatinib, chemotherapy, margetuximab, hormonal therapy, and abemaciclib plus trastuzumab plus fulvestrant, and may offer pertuzumab if the patient has not previously received it. Optimal duration of chemotherapy is at least 4-6 months or until maximum response, depending on toxicity and in the absence of progression. HER2-targeted therapy can continue until time of progression or unacceptable toxicities. For patients with HER2-positive and estrogen receptor-positive or progesterone receptor-positive breast cancer, clinicians may recommend either standard first-line therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy or endocrine therapy alone.Additional information is available at www.asco.org/breast-cancer-guidelines.

Impact of Age on Clinical Outcomes and Efficacy of Adjuvant Dual Anti-HER2 Targeted Therapy.

BACKGROUND: Young age at breast cancer (BC) diagnosis has historically been a rationale for overtreatment. Limited data with short follow-up exist on the prognostic value of age at diagnosis in HER2-positive BC and the benefit of anti-HER2 therapy in young patients. METHODS: APHINITY (NCT01358877) is an international, placebo-controlled, double-blind randomized phase III trial in HER2-positive early BC patients investigating the addition of pertuzumab to adjuvant chemotherapy plus trastuzumab. The prognostic and predictive value of age on invasive disease-free survival (IDFS) as continuous and dichotomous variable (aged 40 years or younger and older than 40 years) was assessed. A subpopulation treatment effect pattern plot analysis was conducted to illustrate possible treatment-effect heterogeneity based on age as a continuous factor. RESULTS: Of 4804 included patients, 768 (16.0%) were aged 40 years or younger at enrollment. Median follow-up was 74 (interquartile range = 62-75) months. Young age was not prognostic either as dichotomous (hazard ratio [HR] = 1.06, 95% confidence interval [CI] = 0.84 to 1.33) or continuous (HR = 1.00, 95% CI = 1.00 to 1.01) variable. Lack of prognostic effect of age was observed irrespective of hormone receptor status and treatment arm. No statistically significant interaction was observed between age and pertuzumab effect (Pinteraction = 0.61). Adding pertuzumab improved IDFS for patients in the young (HR = 0.86, 95% CI = 0.56 to 1.32) and older (HR = 0.75, 95% CI = 0.62 to 0.92) cohorts. Similar results were observed irrespective of hormone receptor status. Subpopulation treatment effect pattern plot analysis confirmed the benefit of pertuzumab in 6-year IDFS across age subpopulations. CONCLUSIONS: In patients with HER2-positive early BC treated with modern anticancer therapies, young age did not demonstrate either prognostic or predictive value, irrespective of hormone receptor status.

Implication of body mass index (BMI) on the biological and clinical effects of endocrine therapy plus abemaciclib as neoadjuvant therapy for early breast cancer patients.

PURPOSE: Inferior overall response rate with abemaciclib plus endocrine therapy was observed in patients with hormone receptor-positive/HER2-negative advanced breast cancer (BC) and BMI ≥ 25. We assessed the impact of baseline BMI on KI67% changes, achievement of complete cell cycle arrest (CCCA), clinical, and radiological responses in patients included in the NEOMONARCH trial. METHODS: Exploratory post hoc analysis of the NEOMONARCH trial was performed. Patients were classified according to baseline BMI into underweight/normal weight (BMI < 25 kg/m2) and overweight/obese (BMI ≥ 25 kg/m2). RESULTS: 222 patients (84.4%) had baseline BMI information available. In the overall cohort, mean Ki67% changes at 2 weeks were similar between the two BMI groups: - 19 (IQR - 27.8 to - 10.4) for patients with BMI < 25 and - 17.2 (IQR - 26.8 to - 11) for patients with BMI ≥ 25 (p = 0.760). There was no statistical difference in patients achieving CCCA after 2 weeks of treatment according to BMI (p = 0.096). Mean Ki67% reduction at 2 weeks was significantly higher for patients receiving abemaciclib plus anastrozole when compared to either anastrozole or abemaciclib alone, regardless of BMI. At the end of treatment, there was no significant difference regarding radiological (p = 0.366) or clinical response (p = 0.261). CONCLUSION: BMI categorized by the threshold of 25 did not significantly impact KI67% changes or clinical and radiological response. Although limited by the small sample size, these results are reassuring that the combination of abemaciclib plus anastrazole appears to be active in the early setting regardless of baseline BMI. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02441946.

Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis.

PURPOSE: Symptoms of treatment-induced menopause negatively affect quality of life and adherence to endocrine therapy of breast cancer (BC) survivors. Nevertheless, the use of systemic hormone replacement therapy (HRT) to mitigate these symptoms may be associated with an increased risk of disease recurrence in these patients. This systematic review and meta-analysis aimed to assess the safety of systemic HRT on risk of disease recurrence in BC survivors. METHODS: A systematic search of PubMed up to April 20, 2021 was conducted to identify randomized controlled trials (RCTs) that investigated the risk of disease recurrence with the use of HRT in BC survivors. A random-effect model was applied to calculate the risk of recurrence, reported as pooled hazard ratio (HR) with 95% confidence intervals (CI). A subgroup analysis was performed to estimate the risk of recurrence according to hormone receptor status. RESULTS: Four RCTs were included in the meta-analysis (n = 4050 patients). Overall, 2022 patients were randomized to receive HRT (estrogen/progestogen combination or tibolone) and 2023 to the control group with placebo or no HRT. HRT significantly increased the risk of BC recurrence compared to placebo (HR 1.46, 95% CI 1.12-1.91, p = 0.006). At the subgroup analysis, the risk of BC recurrence with the use of HRT was significantly increased in patients with hormone receptor-positive disease (HR 1.8, 95% CI 1.15-2.82, p = 0.010) but not in those with hormone receptor-negative tumors (HR 1.19, 95% CI 0.80-1.77, p = 0.390). CONCLUSION: Use of HRT was associated with a detrimental prognostic effect in BC survivors, particularly in those with hormone receptor-positive disease. Alternative interventions to mitigate menopause-related symptoms should be proposed.

Overall survival analyses of female malignancies in Southern Brazil during 2008-2017: A closer look at breast, cervical and ovarian cancer.

Background: The aim of this study was to report the overall survival and baseline factors associated with OS for breast, cervical and ovarian cancer in Florianópolis, Southern Brazil, a region with quality-of-life indicators comparable to high-income countries. Methods: Cohort study was performed from probabilistic record linkage of the Mortality Information System and the Population-based cancer registry of Florianópolis. It was included breasts, cervical and ovarian cancer diagnosis during the period of 2008-2012 with a follow up of 60 months. Cox regression and Kaplan-Meier method were used for associations with overall survival and risk factors. Findings: 1857 cases of the three malignancies were included in the analysis. We identified 202 deaths in breast cancer subjects, 53 for cervical cancer and 51 for ovarian cancer. Metastatic disease at diagnosis was present in 31%, 9.6%, and 55% of the cases, respectively. Overall survival was statistically correlated with age, educational level and stage for breast cancer; age and stage for cervical cancer; age and stage for ovarian cancer. Interpretation: Metastatic disease and age are the main prognostic factors for the malignancies studied, as they were associated with both overall survival and risk of death. Better screening and preventive tests for early diagnosis are needed. Funding: Support of Research and Innovation in the State of Santa Catarina, Research Program for the Unified Health System (FAPESC/MS-DECIT/CNPQ/SES-SC-PPSUS); the Brazilian National Research Council (CNPq); and the Coordination for the Improvement of Higher Education Personnel (CAPES).

Tumour-infiltrating lymphocytes in non-invasive breast cancer: A systematic review and meta-analysis.

BACKGROUND: The role of tumour infiltrating lymphocytes (TILs) as a biomarker in non-invasive breast cancer is unclear. This meta-analysis assessed the prognostic impact of TIL levels in patients with non-invasive breast cancer. METHODS: Systematic literature search was performed to identify studies assessing local recurrence in patients with non-invasive breast cancer according to TIL levels (high vs. low). Subgroup analyses per local recurrence (invasive and non-invasive) were performed. Secondary objectives were the association between TIL levels and non-invasive breast cancer subtypes, age, grade and necrosis. Odds ratios (ORs) and 95% confidence intervals (CI) were extracted from each study and a pooled analysis was conducted with random-effect model. RESULTS: Seven studies (N = 3437) were included in the present meta-analysis. High-TILs were associated with a higher likelihood of local recurrence (invasive or non-invasive, N = 2941; OR 2.05; 95%CI, 1.03-4.08; p = 0.042), although with a lower likelihood of invasive local recurrence (N = 1722; OR 0.69; 95%CI, 0.49-0.99; p = 0.042). High-TIL levels were associated with triple-negative (OR 3.84; 95%CI, 2.23-6.61; p < 0.001) and HER2-positive (OR 6.27; 95%CI, 4.93-7.97; p < 0.001) subtypes, high grade (OR 5.15; 95%CI, 3.69-7.19; p < 0.001) and necrosis (OR 3.09; 95%CI, 2.33-4.10; p < 0.001). CONCLUSIONS: High-TIL levels were associated with more aggressive tumours, a higher likelihood of local recurrence (invasive or non-invasive) but a lower likelihood of invasive local recurrence in patients with non-invasive breast cancer.

Pregnancy After Breast Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Many patients and physicians remain concerned about the potential detrimental effects of pregnancy after breast cancer (BC) in terms of reproductive outcomes and maternal safety. This systematic review and meta-analysis aimed at providing updated evidence on these topics. METHODS: A systematic literature review was conducted to identify studies including patients with a pregnancy after BC (PROSPERO number CRD42020158324). Likelihood of pregnancy after BC, their reproductive outcomes, and maternal safety were assessed. Pooled relative risks, odds ratios (ORs), and hazard ratios (HRs) with 95% CIs were calculated using random effects models. RESULTS: Of 6,462 identified records, 39 were included involving 8,093,401 women from the general population and 112,840 patients with BC of whom 7,505 had a pregnancy after diagnosis. BC survivors were significantly less likely to have a subsequent pregnancy compared with the general population (relative risk, 0.40; 95% CI, 0.32 to 0.49). Risks of caesarean section (OR, 1.14; 95% CI, 1.04 to 1.25), low birth weight (OR, 1.50; 95% CI, 1.31 to 1.73), preterm birth (OR, 1.45; 95% CI, 1.11 to 1.88), and small for gestational age (OR, 1.16; 95% CI, 1.01 to 1.33) were significantly higher in BC survivors, particularly in those with previous chemotherapy exposure, compared with the general population. No significantly increased risk of congenital abnormalities or other reproductive complications were observed. Compared to patients with BC without subsequent pregnancy, those with a pregnancy had better disease-free survival (HR, 0.66; 95% CI, 0.49 to 0.89) and overall survival (HR, 0.56; 95% CI, 0.45 to 0.68). Similar results were observed after correcting for potential confounders and irrespective of patient, tumor, and treatment characteristics, pregnancy outcome, and timing of pregnancy. CONCLUSION: These results provide reassuring evidence on the safety of conceiving in BC survivors. Patients' pregnancy desire should be considered a crucial component of their survivorship care plan.

Evidence-based approaches for the management of side-effects of adjuvant endocrine therapy in patients with breast cancer.

The growing availability of more effective therapies has contributed to an increased survival of patients with breast cancer. In hormone receptor-positive early disease, increased survival is strongly correlated with the use of adjuvant endocrine therapy, but this therapy can cause side-effects that have major consequences in terms of treatment adherence and patients' quality of life. In premenopausal breast cancer survivors, these side-effects might be even more prominent due to the abrupt suppression of oestrogen associated with the most intense endocrine therapies. An important ambition of cancer care in the 21st century is to recover pre-cancer quality of life and emotional and social functions, which is only possible through the mitigation of the side-effects of anticancer treatments. This Review presents a comprehensive summary of the efficacy and safety data of the available interventions (hormonal and non-hormonal pharmacological strategies, non-pharmacological approaches, and complementary and alternative medicine) to control selected side-effects associated with adjuvant endocrine therapy (hot flashes, sexual dysfunction, weight gain, musculoskeletal symptoms, and fatigue), providing updated, evidence-based approaches for their management.

Clinical outcomes of platinum-based chemotherapy in patients with advanced breast cancer: An 11-year single institutional experience.

BACKGROUND/METHODS: Although the prognosis of metastatic breast cancer (BC) has improved, some patients still develop high burden metastases or visceral crisis (VC) and polychemotherapy is commonly used in these cases. Data reporting the real effectiveness of this strategy are scanty. Therefore, the outcomes of patients with metastatic BC treated with platinum-based chemotherapy (P-ChT) at the Jules Bordet Institute during the period of January 2008 and December 2018 were retrospectively reviewed. The presence of VC was defined according to ABC 4 criteria. RESULTS: 441 patients were identified: visceral metastases were observed in 430 (97.5%) while 261 (59.2%) presented VC. As for metastatic BC subtype, 255 (57.8%) had ER-positive/HER2-negative, 41 (9.3%) ER-positive/HER2-positive, 34 (7.7%) ER-negative/HER2-positive and 111 (25.1%) triple-negative BC. Median number of prior treatment lines was 3.8 (0-12). Median OS with P-ChT in the entire cohort was 6.13 months. Patients with VC had lower OS than patients without VC (8.6 vs 3.7 months; p < 0.001). On multivariate analysis, the variables correlated with worse OS were hyperbilirubinemia (HR 1.90; 95% CI 1.34-2.75), ECOG ≥2 (HR 1.77; 95% CI 1.13-2.78) and ECOG ≥3 (HR 2.52; 95% CI 1.48-4.28), and >3 previous treatment lines (HR 2.27; 95% CI 1.53-3.21). Of the 261 patients with VC, 106 (40.5%) presented a resolution of the VC which correlated with better OS (9.3 vs 2.0 months, HR 0.27; 95% CI 0.21-0.36). CONCLUSION: Patients who overcome VC benefit from P-ChT with OS similar to patients without VC. In this analysis, hyperbilirubinemia, poor ECOG and >3 previous treatment lines were significant prognostic factors in the overall study population.

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.