Psychosocial and supportive care concerns of young women living with advanced breast cancer: baseline findings from a prospective virtual support intervention study.

PURPOSE: Adolescent and young adults (AYAs) with metastatic breast cancer (MBC) experience high physical and psychosocial burdens compounded by a disrupted life trajectory. We sought to determine the psychosocial and supportive care concerns of this population to better understand and address unmet needs. METHODS: AYAs diagnosed with MBC (18-39 years) participating in a prospective interventional study (Young, Empowered, and Strong) at Dana-Farber Cancer Institute completed an electronic survey following enrollment. Measures evaluated sociodemographics, health behaviors, quality of life, and symptoms, among others. We used two-sided Fisher's exact tests to determine associations between concerns (e.g., cancer progression, side effects, lifestyle, finances, fertility) and demographic variables. RESULTS: Among 77 participants enrolled from 9/2020-12/2022, average age at MBC diagnosis and survey was 35.9 (range: 22-39) and 38.3 years (range: 27-46), respectively. Most were non-Hispanic white (83.8%) and 40.3% reported their diagnosis caused some financial problems. Many were concerned about fertility (27.0%), long-term treatment side effects (67.6%), exercise (61.6%), and diet (54.1%). Select concerns varied significantly by age, race/ethnicity, and education. Younger women at survey reported greater concern about familial cancer risk (p = 0.028). Women from minority racial/ethnic groups more frequently reported issues talking about their cancer to family/friends (p = 0.040) while those with more education were more frequently concerned with long-term effects of cancer on their health (p = 0.021). CONCLUSION: Young women living with MBC frequently report psychosocial, health, and cancer management concerns. Tailoring supportive care and communications to address prevalent concerns including disease progression and treatment side effects may optimize wellbeing.

Adjuvant Olaparib for Germline BRCA Carriers With HER2-Negative Early Breast Cancer: Evidence and Controversies.

In the OlympiA study, 1 year of adjuvant olaparib significantly extended invasive disease-free survival and overall survival. The benefit was consistent across subgroups, and this regimen is now recommended after chemotherapy for germline BRCA1/2 mutation (gBRCA1/2m) carriers with high-risk, HER2-negative early breast cancer. However, the integration of olaparib in the landscape of agents currently available in the post(neo)adjuvant setting-ie, pembrolizumab, abemaciclib, and capecitabine-is challenging, as there are no data suggesting how to select, sequence, and/or combine these therapeutic approaches. Furthermore, it is unclear how to best identify additional patients who could benefit from adjuvant olaparib beyond the original OlympiA criteria. Since it is unlikely that new clinical trials will answer these questions, recommendations for clinical practice can be made through indirect evidence. In this article, we review available data that could help guide treatment decisions for gBRCA1/2m carriers with high-risk, early-stage breast cancer.

Impact of Neoadjuvant Paclitaxel/Trastuzumab/Pertuzumab on Breast Tumor Downsizing for Patients with HER2+ Breast Cancer: Single-Arm Prospective Clinical Trial.

BACKGROUND: The impact of abbreviated neoadjuvant regimens for HER2+ breast cancer on rates of breast conservation therapy (BCT) is unclear. We aimed to determine BCT rates in a single-arm prospective trial of neoadjuvant paclitaxel/trastuzumab/pertuzumab (THP) in patients with stage II or III HER2+ breast cancer. STUDY DESIGN: BCT eligibility was prospectively recorded before and after THP. Pre- and posttreatment mammogram and breast ultrasound were required; breast MRI was encouraged. Patients with a large tumor to breast size ratio were eligible for downsizing. Multifocal/multicentric tumors, extensive calcifications, and contraindications to radiation were considered BCT contraindications. RESULTS: Overall, 92 patients who received neoadjuvant THP on trial were included. At presentation, 39 (42.4%) were considered eligible for BCT and 53 (57.6%) were not. BCT-eligible patients were older (median 54 vs 47 years, respectively; p = 0.006) and had smaller tumors by palpation (median 2.5 vs 3 cm, respectively; p = 0.004). Of 53 BCT-ineligible patients, 28 were candidates for tumor downsizing, whereas 25 had contraindications to BCT. Overall, 51 (55.4%) patients underwent BCT. Of the 28 patients who were candidates for downsizing, 22 (78.6%) became BCT-eligible after THP and 18 of 22 (81.8%) underwent BCT. In total, 44 of 92 (47.8%) patients experienced breast pathologic complete response (ypT0), including 11 of 25 (44.0%) patients with BCT contraindications at presentation. CONCLUSIONS: De-escalated neoadjuvant systemic therapy led to high BCT rates in this cohort. The impact of de-escalated systemic therapy on local therapy and outcomes in early stage HER2+ breast cancer warrants further investigation.

Adjuvant endocrine therapy non-initiation and non-persistence in young women with early-stage breast cancer.

PURPOSE: Characterizing oral adjuvant endocrine therapy (ET) non-initiation and non-persistence in young women with breast cancer can inform strategies to improve overall adherence in this population. METHODS: We identified 693 women with hormone receptor-positive, stage I-III breast cancer enrolled in a cohort of women diagnosed with breast cancer at age ≤ 40 years. Women were classified as non-initiators if they did not report taking ET in the 18 months after diagnosis. Women who initiated but did not report taking ET subsequently (through 5-year post-diagnosis) were categorized as non-persistent. We assessed ET decision-making and used logistic regression to identify factors associated with non-initiation/non-persistence and to evaluate the association between non-persistence and recurrence. RESULTS: By 18 months, 9% had not initiated ET. Black women had higher odds and women with a college degree had lower odds of non-initiation. Among 607 women who initiated, 20% were non-persistent. Younger age, being married/partnered, and reporting more weight problems were associated with higher odds of non-persistence; receipt of chemotherapy and greater hot flash and vaginal symptom burden were associated with lower odds of non-persistence. Adjusting for age and clinical characteristics, non-persistence was associated with lower odds of recurrence. Women who initiated were more likely to report shared decision-making than non-initiators (57% vs. 38%, p = 0.049), while women who were non-persistent were less likely to indicate high confidence with the decision than women who were persistent (40% vs. 63%, p < 0.001). CONCLUSION: Interventions to improve ET decision-making may facilitate initiation and address barriers to adherence in young breast cancer survivors. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , NCT01468246.

Coping strategies and anxiety in young breast cancer survivors.

PURPOSE: We sought to describe coping strategies reported by young breast cancer survivors and evaluate the relationship between utilization of specific coping strategies and anxiety in survivorship. METHODS: Participants enrolled in The Young Women's Breast Cancer Study, a multi-center, cohort of women diagnosed with breast cancer at age ≤ 40 years, completed surveys that assessed demographics, coping strategies (reported at 6-month post-enrollment and 18-month post-diagnosis), and anxiety (2 years post-diagnosis). We used univariable and multivariable logistic regression to examine the relationship between coping strategies and anxiety. RESULTS: A total of 833 women with stage 0-3 breast cancer were included in the analysis; median age at diagnosis was 37 (range: 17-40) years. Social supports were the most commonly reported coping strategies, with the majority reporting moderate or greater use of emotional support from a partner (90%), parents (78%), other family (79%), and reliance on friends (88%) at both 6 and 18 months. In multivariable analyses, those with moderate or greater reliance on emotional support from other family (odds ratio (OR): 0.37, 95% confidence ratio (CI): 0.22-0.63) at 18 months were less likely to have anxiety at 2 years, while those with moderate or greater reliance on alcohol/drug use (OR: 1.83, 95%CI: 1.12-3.00) and taking care of others (OR: 1.90, 95%CI: 1.04-3.45) to cope were more likely to have anxiety. CONCLUSION: Young breast cancer survivors rely heavily on support from family and friends. Our findings underscore the importance of considering patients' social networks when developing interventions targeting coping in survivorship. CLINICAL TRIAL REGISTRATION NUMBER: NCT01468246 (first posted November 9, 2011).

Body weight changes and associated predictors in a prospective cohort of young breast cancer survivors.

BACKGROUND: Weight gain after a breast cancer diagnosis is common and is associated with inferior outcomes. Young survivors may be especially susceptible to weight changes given the impact of treatment on menopausal status. METHODS: The authors identified women who were diagnosed with stage 0 to III breast cancer at age 40 years or younger between 2006 and 2016 from a multicenter prospective cohort. Self-reported weight was collected at diagnosis and at 1 year and 3 years postdiagnosis. Tumor and treatment data were obtained from medical records and patient surveys. Multinomial logistic regression was used to identify the factors associated with weight gain (≥5%) or weight loss (≥5%) versus stable weight at 1 year and 3 years postdiagnosis. RESULTS: The cohort included 956 women with a median age of 37 years at diagnosis. Mean weight significantly increased over time from 66.54 ± 14.85 kg at baseline to 67.33 ± 15.53 and 67.77 ± 14.65 kg at 1 year and 3 years, respectively (p ≤ .001 for both comparisons). The proportion of women experiencing ≥5% weight gain increased from 24.8% at 1 year to 33.9% at 3 years. At 1 year, less self-perceived financial comfort, Black race, and stage III disease were significantly associated with weight gain; at 3 years, only less self-perceived financial comfort remained significant. Baseline overweight or obesity was significantly associated with weight loss at both time points. Chemotherapy, endocrine therapy, and treatment-related menopause were not associated with weight change. CONCLUSIONS: One third of young breast cancer survivors experienced clinically significant weight gain 3 years after diagnosis; however, treatment-related associations were not observed. Age-appropriate lifestyle interventions, including the reduction of financial barriers, are needed to prevent weight gain in this high-risk population.

Acceptability of a companion patient guide to support expert consensus guidelines on surveillance mammography in older breast cancer survivors.

PURPOSE: To support shared decision-making, patient-facing resources are needed to complement recently published guidelines on approaches for surveillance mammography in breast cancer survivors aged ≥ 75 or with < 10-year life expectancy. We created a patient guide to facilitate discussions about surveillance mammography in older breast cancer survivors. METHODS: The "Are Mammograms Still Right for Me?" guide estimates future ipsilateral and contralateral breast (in-breast) cancer risks, general health, and the potential benefits/harms of mammography, with prompts for discussion. We conducted in-clinic acceptability testing of the guide by survivors and their clinicians at a National Cancer Institute-designated comprehensive cancer center, including two community practices. Patients and clinicians received the guide ahead of a clinic visit and surveyed patients (pre-/post-visit) and clinicians (post-visit). Acceptability was defined as ≥ 75% of patients and clinicians reporting that the guide (a) should be recommended to others, (b) is clear, (c) is helpful, and (d) contains a suitable amount of information. We also elicited feedback on usability and mammography intentions. RESULTS: We enrolled 45 patients and their 21 clinicians. Among those responding in post-visit surveys, 33/37 (89%) patients and 15/16 (94%) clinicians would recommend the guide to others; 33/37 (89%) patients and 15/16 (94%) clinicians felt everything/most things were clear. All other pre-specified acceptability criteria were met. Most patients reported strong intentions for mammography (100% pre-visit, 98% post-visit). CONCLUSION: Oncology clinicians and older breast cancer survivors found a guide to inform mammography decision-making acceptable and clear. A multisite clinical trial is needed to assess the guide's impact mammography utilization. TRIAL REGISTRATION: ClinicalTrials.gov-NCT03865654, posted March 7, 2019.

A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer.

De-escalating adjuvant therapy following pathologic complete response (pCR) to an abbreviated neoadjuvant regimen in human epidermal growth factor receptor 2-positive (HER2+) breast cancer is the focus of international research efforts. However, the feasibility of this approach and its appeal to patients and providers had not been formally investigated. We aimed to assess adherence to de-escalated adjuvant antibody doublet therapy (trastuzumab and pertuzumab [HP], without chemotherapy) among patients with pCR following neoadjuvant paclitaxel/HP (THP). In this single-arm prospective trial, patients with treatment-naïve stage II-III HER2+ breast cancer received neoadjuvant weekly paclitaxel ×12 and HP every 3 weeks ×4. The primary endpoint was receipt of adjuvant non-HER2-directed cytotoxic chemotherapy. Ninety-eight patients received ≥1 dose of THP on study. Patients had median age of 50 years, 86% had stage II tumors, and 34% were hormone receptor-negative. Five patients had incomplete clinical response following THP and received doxorubicin and cyclophosphamide before surgery; they were classified as non-pCR and censored from further analyses. The overall pCR rate was 56.7%. Among patients with pCR, the adherence rate to de-escalated antibody-only therapy (HP) was 98.2% (95% CI 90.3-100.0%), and the primary feasibility endpoint was reached. The majority of patients felt positive or neutral about their adjuvant treatment plans. With brief follow-up (median 19.1 months), there were no breast cancer recurrences. De-escalation of adjuvant chemotherapy among patients who experience pCR in early-stage HER2+ breast cancer is a practicable approach for both patients and physicians. Planned and ongoing prospective trials will determine the long-term efficacy of this approach.Trial registration clinicaltrials.gov, NCT03716180, https://clinicaltrials.gov/ct2/show/NCT03716180 .

Somatic and Germline Genomic Alterations in Very Young Women with Breast Cancer.

PURPOSE: Young age at breast cancer diagnosis correlates with unfavorable clinicopathologic features and worse outcomes compared with older women. Understanding biological differences between breast tumors in young versus older women may lead to better therapeutic approaches for younger patients. EXPERIMENTAL DESIGN: We identified 100 patients ≤35 years old at nonmetastatic breast cancer diagnosis who participated in the prospective Young Women's Breast Cancer Study cohort. Tumors were assigned a surrogate intrinsic subtype based on receptor status and grade. Whole-exome sequencing of tumor and germline samples was performed. Genomic alterations were compared with older women (≥45 years old) in The Cancer Genome Atlas, according to intrinsic subtype. RESULTS: Ninety-three tumors from 92 patients were successfully sequenced. Median age was 32.5 years; 52.7% of tumors were hormone receptor-positive/HER2-negative, 28.0% HER2-positive, and 16.1% triple-negative. Comparison of young to older women (median age 61 years) with luminal A tumors (N = 28 young women) revealed three significant differences: PIK3CA alterations were more common in older patients, whereas GATA3 and ARID1A alterations were more common in young patients. No significant genomic differences were found comparing age groups in other intrinsic subtypes. Twenty-two patients (23.9%) in the Young Women's Study cohort carried a pathogenic germline variant, most commonly (13 patients, 14.1%) in BRCA1/2. CONCLUSIONS: Somatic alterations in three genes (PIK3CA, GATA3, and ARID1A) occur at different frequencies in young versus older women with luminal A breast cancer. Additional investigation of these genes and associated pathways could delineate biological susceptibilities and improve treatment options for young patients with breast cancer. See related commentary by Yehia and Eng, p. 2209.

Surgical Treatment After Neoadjuvant Systemic Therapy in Young Women With Breast Cancer: Results From a Prospective Cohort Study.

OBJECTIVE: We aimed to investigate eligibility for breast conserving surgery (BCS) pre- and post-neoadjuvant systemic therapy (NST), and trends in the surgical treatment of young breast cancer patients. BACKGROUND: Young women with breast cancer are more likely to present with larger tumors and aggressive phenotypes, and may benefit from NST. Little is known about how response to NST influences surgical decisions in young women. METHODS: The Young Women's Breast Cancer Study, a multicenter prospective cohort of women diagnosed with breast cancer at age ≤40, enrolled 1302 patients from 2006 to 2016. Disease characteristics, surgical recommendations, and reasons for choosing mastectomy among BCS-eligible patients were obtained through the medical record. Trends in use of NST, rate of clinical and pathologic complete response, and surgery were also assessed. RESULTS: Of 1117 women with unilateral stage I-III breast cancer, 315 (28%) received NST. Pre-NST, 26% were BCS eligible, 17% were borderline eligible, and 55% were ineligible. After NST, BCS eligibility increased from 26% to 42% (P < 0.0001). Among BCS-eligible patients after NST (n = 133), 41% chose mastectomy with reasons being patient preference (53%), BRCA or TP53 mutation (35%), and family history (5%). From 2006 to 2016, the rates of NST (P = 0.0012), clinical complete response (P < 0.0001), and bilateral mastectomy (P < 0.0001) increased, but the rate of BCS did not increase (P = 0.34). CONCLUSION: While the proportion of young women eligible for BCS increased after NST, many patients chose mastectomy, suggesting that surgical decisions are often driven by factors beyond extent of disease and treatment response.

Trajectories of fear of cancer recurrence in young breast cancer survivors.

BACKGROUND: Fear of cancer recurrence (FCR) is more intense in younger women. Because FCR is a powerful determinant of quality of life, identifying those at risk for persistently elevated FCR can inform timing of interventions. METHODS: A total of 965 women with stage 0 to stage III breast cancer enrolled in the Young Women's Breast Cancer Study, a prospective cohort of women diagnosed with breast cancer at age ≤40 years, completed the 3-item Lasry Fear of Recurrence Index. Group-based trajectory modeling was used to classify distinct FCR patterns from baseline through 5 years post-diagnosis. Multinomial logistic regression was used to identify patient, disease, and treatment characteristics associated with each trajectory. RESULTS: Five FCR trajectories were identified with the majority of participants having moderate (33.1%) or high FCR (27.6%) that improved over time. A total of 6.9% participants had moderate FCR that worsened, whereas 21.7% had high FCR at baseline that remained high throughout. In the fully adjusted multinomial model, stages II and III (vs stage I) were associated with lower odds (of being in the high/stable trajectory). White (vs non-White) were associated with higher odds of being in a trajectory that improved over time. CONCLUSIONS: Although FCR improves over time for many young women with breast cancer, approximately one-third had FCR that was severe and did not improve or worsened over 5 years after diagnosis. Ongoing monitoring is warranted, with early referral to mental health professionals indicated for those at highest risk for unresolved FCR. LAY SUMMARY: Fear of recurrence is common among young women with breast cancer. The authors followed a large cohort of young women diagnosed with breast cancer when they were 40 years of age and younger, and found 5 distinct trajectories that show moderate and severe fears do not always improve over time and may require targeted mental health intervention.

Clinicopathological features and BRCA1 and BRCA2 mutation status in a prospective cohort of young women with breast cancer.

BACKGROUND: Breast cancer in young women is more likely to have higher risk features and be associated with germline BRCA1/BRCA2 mutations. We present the clinicopathologic features of breast cancers in a prospective cohort of young women, and associations between surrogate molecular subtype and BRCA1/BRCA2 mutation status. METHODS: Histopathological features, biomarker status, tumour stage and BRCA status were collected. Invasive tumours were categorised as luminal A-like (ER + and/or PR + , HER2-, grade 1/2), luminal B-like (ER + and/or PR + , HER2 + , or ER + and/or PR + , HER2-, and grade 3), HER2-enriched (ER/PR-, HER2 + ) or triple-negative. RESULTS: In all, 57.3% (654/1143) of invasive tumours were high grade. In total, 32.9% were luminal A-like, 42.4% luminal B-like, 8.3% HER2-enriched, and 16.4% triple-negative. Among different age groups, there were no differences in molecular phenotype, stage, grade or histopathology. 11% (131) of tumours were from BRCA mutation carriers; 64.1% BRCA1 (63.1% triple-negative), and 35.9% BRCA2 (55.3% luminal B-like). DISCUSSION: The opportunity to provide comparisons across young age groups, BRCA mutation status, surrogate molecular phenotype, and the identification of more aggressive hormone receptor-positive phenotypes in this population provides direction for future work to further understand and improve disparate outcomes for young women with luminal B-like cancers, particularly BRCA2-associated cancers, with potential implications for tailored prevention and treatment.

Young, Empowered and Strong: A Web-Based Education and Supportive Care Intervention for Young Women With Breast Cancer Across the Care Continuum.

PURPOSE: Patient-centered digital interventions may help empower young women to self-manage symptoms and psychosocial concerns and support informational needs often unaddressed in clinic. METHODS: Young, Empowered and Strong (YES) is an interactive web-based intervention designed to engage young women with personalized education and symptom self-management resources on the basis of responses to patient-reported outcome-based questionnaires. We piloted YES among young women (< 45 years) with newly diagnosed early breast cancer (EBC) or metastatic breast cancer (MBC) and breast cancer survivors (BCSs). Assessments were deployed weekly (EBC and MBC) or every 4 weeks (BCSs) over 12 weeks. At study completion, use, feasibility, and acceptability of YES were evaluated via a survey and semistructured interview. RESULTS: Thirty women were enrolled between April and June 2019: 10 EBC, 10 BCSs, and 10 MBC. The mean age at diagnosis and enrollment was 36 (range 25-44) and 39 (range 31-44) years, respectively. Most participants were actively treated (96%, 27 of 28) with endocrine therapy (54%, 15 of 28) or chemotherapy (43%, 12 of 28). Overall, 61% (180 of 296) of assessments were completed (EBC: 70%, BCSs: 63%, and MBC: 52%). Of 37 patient-reported outcome and need domains, the most frequently triggered were sexual health (EBC: 90%, BCSs: 90%, and MBC: 90%), anxiety (EBC: 80%, BCSs: 90%, and MBC: 90%), stress and mindfulness (EBC: 80%, BCSs: 90%, and MBC: 90%), and fatigue (EBC: 90%, BCSs: 80%, and MBC: 90%). On postpilot survey, participants reported that YES helped them to learn (50%, 7 of 14), monitor (43%, 6 of 14), and manage (57%, 8 of 14) their symptoms. CONCLUSION: YES is a feasible and acceptable digital intervention to support young women across the breast cancer care continuum. The nearly universal triggering of sexual and mental health needs suggests suboptimal management in the clinical setting and the potential for self-management through a digital platform.

Treatment-related amenorrhea in a modern, prospective cohort study of young women with breast cancer.

Young women with breast cancer experience unique treatment and survivorship issues centering on treatment-related amenorrhea (TRA), including fertility preservation and management of ovarian function as endocrine therapy. The Young Women's Breast Cancer Study (YWS) is a multi-center, prospective cohort study of women diagnosed at age ≤40, enrolled from 2006 to 2016. Menstrual outcomes were self-reported on serial surveys. We evaluated factors associated with TRA using logistic regression. One year post-diagnosis, 286/789 (36.2%) experienced TRA, yet most resumed menses (2-year TRA: 120/699; 17.2%). Features associated with 1-year TRA included older age (OR≤30vs36-40 = 0.29 (0.17-0.48), OR31-35vs36-40 = 0.67 (0.46-0.94), p = 0.02); normal body mass index (BMI) (OR≥25vs18.5-24. =0.59 (0.41-0.83), p < 0.01); chemotherapy (ORchemo vs no chemo = 5.55 (3.60-8.82), p < 0.01); and tamoxifen (OR = 1.55 (1.11-2.16), p = 0.01). TRA rates were similar across most standard regimens (docetaxel/carboplatin/trastuzumab +/- pertuzumab: 55.6%; docetaxel/cyclophosphamide +/- trastuzumab/pertuzumab: 41.8%; doxorubicin/cyclophosphamide/paclitaxel +/- trastuzumab/pertuzumab: 44.1%; but numerically lower with AC alone (25%) or paclitaxel/trastuzumab (11.1%). Among young women with breast cancer, lower BMI appears to be an independent predictor of TRA. This finding has important implications for interpretation of prior studies, future research, and patient care in our increasingly obese population. Additionally, these data describe TRA associated with use of docetaxel/cyclophosphamide, which is increasingly being used in lieu of anthracycline-containing regimens. Collectively, these data can be used to inform use of fertility preservation strategies for women who need to undergo treatment as well as the potential need for ovarian suppression following modern chemotherapy for young women with estrogen-receptor-positive breast cancer.Clinical trial registration: www.clinicaltrials.gov, NCT01468246.

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.

The impact of fertility preservation on the timing of breast cancer treatment, recurrence, and survival.

BACKGROUND: Many young women with breast cancer undergo fertility preservation (FP) before cancer treatment. This study examined the impact of FP on breast cancer outcomes. METHODS: The authors performed a retrospective cohort study of 272 women aged 20 to 45 years with newly diagnosed stage 0 to III breast cancer who underwent an FP consultation between 2005 and 2017. Among these women, 123 (45.2%) underwent FP (fertility preservation-positive [FP+]). The remaining 149 women did not undergo FP (fertility preservation-negative [FP-]). RESULTS: The characteristics at enrollment were similar with the exception of ethnicity (FP+, 87.8% White; FP-, 67.8% White; P = .002) and BRCA status (FP+, 27.7% BRCA+; FP-, 15.5% BRCA+; P = .021). The median follow-up was approximately 4 years. Women who underwent FP had longer times to first treatment (FP+, 37 days; FP-, 31 days; adjusted hazard ratio [aHR], 0.74; confidence interval [CI], 0.56-0.99) and neoadjuvant chemotherapy (FP+, 36 days; FP-, 26 days; aHR, 0.41; CI, 0.24-0.68) and from surgery to adjuvant chemotherapy (FP+, 41 days; FP-, 33 days; aHR, 0.58; CI, 0.38-0.90). Adjusted 3- and 5-year invasive disease-free survival (IDFS) rates were comparable between the 2 groups (3-year IDFS: FP+, 85.4%; FP-, 79.4%; P = .411; 5-year IDFS: FP+, 73.7%; FP-, 67.1%; P = .288). Similarly, no difference in overall survival (OS) was observed between the 2 groups (3-year OS: FP+, 95.5%; FP-, 93.5%; P = .854; 5-year OS: FP+, 84.2%; FP-, 81.4%; P = .700). CONCLUSIONS: FP after a breast cancer diagnosis delays the time to treatment by a small amount, but this delay does not lead to inferior IDFS or OS.

Impact of fertility concerns on endocrine therapy decisions in young breast cancer survivors.

BACKGROUND: The diagnosis and treatment of breast cancer can have profound effects on a young woman's family planning and fertility, particularly among women with hormone receptor-positive breast cancer. METHODS: The Young Women's Breast Cancer Study was a multicenter cohort of women aged 40 years or younger and newly diagnosed with breast cancer from 2006 to 2016. Surveys included assessments of fertility concerns, endocrine therapy (ET) preferences, and use. Characteristics were compared between women who reported that fertility concerns affected ET decisions and those who did not. Logistic regression was used to identify factors associated with having an ET decision affected by fertility concerns. RESULTS: Of 643 eligible women with hormone receptor-positive, stage I to III breast cancer, one-third (213 of 643) indicated that fertility concerns affected ET decisions. In a multivariable analysis, only parity at diagnosis was significantly associated with fertility concerns affecting ET decisions (odds ratio for nulliparous vs ≥2 children, 6.96; 95% confidence interval, 4.09-11.83; odds ratio for 1 vs ≥2 children, 5.30; 95% confidence interval, 3.03-9.87). Noninitiation/nonpersistence was higher among women with fertility concerns versus those without fertility concerns (40% vs 20%; P < .0001). Among women with fertility-related ET concerns, 7% (15 of 213) did not initiate ET, and 33% (70 of 213) were nonpersistent over 5 years of follow-up. Of these women, 66% (56 of 85) reported 1 or more pregnancies or pregnancy attempts; 27% (15 of 56) had resumed ET at the last available follow-up through 5 years. CONCLUSIONS: Concern about fertility is a contributor to adjuvant ET decisions among a substantial proportion of young breast cancer survivors. Ensuring family planning is addressed in the setting of ET recommendations should be a priority throughout the cancer care continuum.

Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants.

Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR-]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I-III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60-0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94-2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients' counseling on treatment, prevention, and surveillance strategies.

Utility of the 21-Gene Recurrence Score in Node-Positive Breast Cancer.

The 21-gene Recurrence Score (RS) assay has been validated as both a prognostic and predictive tool in node-negative (pN0), estrogen receptor-positive (ER+), HER2-negative (HER2-) breast cancer. A large body of evidence supports the clinical utility of the RS in the node positive (pN+) population as well. Retrospective analyses of archived tissue from multiple clinical trials have found the RS to be prognostic in both endocrine therapy (ET)-treated and chemotherapy-treated patient with pN+ disease. Distribution of RS results in pN+ patients have also been consistent with those of pN0 populations. Data from the SWOG 8814 trial and large population-based registries further support the prognostic and potential predictive value of the RS. Specifically, patients with 1 to 3 positive nodes and RS less than 18 derived negligible benefit from adjuvant chemotherapy in these studies. In the prospective West German Study Group PlanB and ADAPT trials, pN+ patients with RS less than 11 and RS 25 or less, respectively, who were treated with ET alone experienced excellent outcomes. Finally, 5-year results of the RxPONDER clinical trial randomizing patients with 1 to 3 positive nodes and RS 25 or less to ET alone vs ET plus chemotherapy confirmed an absence of chemotherapy benefit in postmenopausal patients. Clinical practice guidelines support use of the RS in the pN+, ER+/HER2- population, and many institutions have adopted the RS to guide clinical decisionmaking, resulting in a net reduction of adjuvant chemotherapy use. This review highlights the existing data supporting the prognostic and predictive ability of the RS in pN+ disease, current practice patterns related to RS use in this population, and emerging applications.