Conception and pregnancy among women with a live birth after breast cancer treatment: A survey study of young breast cancer survivors.

BACKGROUND: Breast cancer (BC) is the most common malignancy in women of reproductive age. This study sought to explore the postcancer conception and pregnancy experience of young BC survivors to inform counseling. METHODS: In the Young Women's Breast Cancer Study (NCT01468246), a multicenter, prospective cohort, participants diagnosed at age ≤40 years with stage 0-III BC who reported ≥1 postdiagnosis live birth were sent an investigator-developed survey. RESULTS: Of 119 eligible women, 94 (79%) completed the survey. Median age at diagnosis was 32 years (range, 17-40) and at first postdiagnosis delivery was 38 years (range, 29-47). Most had stage I or II (77%) and HR+ (78%) BC; 51% were nulligravida at diagnosis. After BC treatment, most (62%) conceived naturally, though 38% used assisted reproductive technology, 74% of whom first attempted natural conception for a median of 9 months (range, 2-48). Among women with a known inherited pathogenic variant (n = 20), two underwent preimplantation genetic testing. Of 59 women on endocrine therapy before pregnancy, 26% did not resume treatment. Hypertensive disorders of pregnancy (20%) was the most common obstetrical condition. Nine percent of newborns required neonatal intensive care unit admission and 9% had low birth weight. CONCLUSION: Among women with live births after BC treatment, most conceived naturally and having a history of BC did not appear to negatively impact pregnancy complications, though the high rate of hypertensive disorders of pregnancy warrants further investigation. The prolonged period of attempting natural conception for some survivors suggests the potential need for improved understanding and counseling surrounding family planning goals after BC.

Characterization of HER2-low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study.

BACKGROUND: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset. METHODS: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05. RESULTS: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor-positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p < .001), hormone receptor-positive (p < .001), and node-positive (p = .003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p < .001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64-0.95) and overall survival (HR, 0.65; 95% CI, 0.46-0.93) in the TN subgroup. Luminal A-like tumors in HER2-low (p = .014) and TN and luminal A-like in HER2-0 (p = .019) showed the worst DFS. CONCLUSIONS: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis.

Second primary non-breast cancers in young breast cancer survivors.

PURPOSE: We evaluated the incidence, timing, and risk factors for second primary non-breast cancers (SPNBC) among young breast cancer (BC) survivors. METHODS: This study included participants of the Young Women's BC Study (YWS) who were diagnosed with stage 0-III BC between 2006 and 2016 and age 40 or younger at diagnosis (N = 1,230). Patient characteristics, treatment information, and clinical events were collected via serial surveys. Tumor and treatment data were obtained from medical record review. Five- and 10-year risks of SPNBCs were estimated via the cumulative incidence function, considering death, metastasis, or second primary BC as competing events. Fine and Gray subdistribution hazard models estimated subdistribution hazard ratios (sHRs) and 95% confidence intervals (CI) for SPNBC risk based on risk factors including demographics, germline genetics, primary BC characteristics, and treatments. RESULTS: Among 1,230 women, over a median follow-up of 10.1 years, 47 patients (4%) developed an SPNBC. Types of malignancy included melanoma (n = 10), thyroid (n = 10), ovarian (n = 4), sarcoma (n = 4), uterine (n = 3), rectal (n = 3), bladder (n = 2), cervical (n = 2), head/neck (n = 2), lung (n = 2), lymphoma (n = 2), pancreatic (n = 2), and renal (n = 1). Five and 10-year cumulative incidence were 1.4% and 3.2%, respectively. Median time between primary BC and SPNBC was 7.3 years. No patient factors, primary tumor characteristics, or treatments were statistically significantly associated with SPNBC in univariable or multivariable models. CONCLUSION: In this population, five-year cumulative incidence was higher than that reported among healthy women under 50 years of age, highlighting the importance of long-term surveillance for new non-breast cancers in young adult BC survivors.

Risk of first recurrence after treatment in a population-based cohort of young women with breast cancer.

PURPOSE: Breast cancer (BC) in women under 45 is rare yet often aggressive. We aim to analyze loco-regional recurrences (LR), distant recurrences (DR), second breast cancers, and mortality in young BC patients. METHODS: We enrolled 776 women with non-metastatic BC ≤45 years diagnosed from 1970 to 2012. Variables included age, family history, tumor stage/grade, and treatment. We used multivariate Cox regression and competing risk models. RESULTS: Among the participants, 37.0% were diagnosed before the age of 40. Most had stage I or II, grade II, ER- and PR-positive, HER2-negative tumors. Over a median follow-up of 8.7 years, 10.1% experienced LR, 13.7% developed DR, and 10.8% died, primarily due to BC. The majority of recurrences occurred within the first five years. Older age (>40) significantly reduced the risk of LR and DR. Advanced disease stage, certain surgical strategies, and positive margins increased DR risk. In the cohort diagnosed between 2001 and 2012, recent diagnosis, triple-negative cancer, and hormonal therapy were associated with reduced LR risk. Breast-conserving surgery appeared to offer protective effects against DR. CONCLUSION: This study highlights that BC in young women carries a significant risk of early recurrence, with age, tumor characteristics, and treatment modalities influencing outcomes. The findings emphasize the need for tailored treatment strategies for young BC patients, focusing on surgical precision and aggressive adjuvant therapy for high-risk cases. This research contributes valuable insights into managing BC in younger patients, aiding in improving long-term outcomes.

Suboptimal use of ovarian function suppression in very young women with early breast cancer: a real-world data study.

PURPOSE: The incidence of breast cancer in young women (BCYW) has increased in recent decades. Malignant disease in this subset is characterized by its aggressiveness and poor prognosis. Ovarian function suppression (OFS) in these patients improves survival especially in hormone receptor-positive (HR +) cases. The Regan Composite Risk (RCR) is a prognostic tool to identify high-risk HR + BC candidates for OFS. Our study sought to characterize a Chilean cohort of early HR + BCYW assessing the use of OFS and its related prognosis and the utility of RCR in our patients. METHODS: This was a retrospective population cohort study that included ≤ 35-year-old early HR + /human epidermal growth factor receptor 2 -negative (HER2-) BC patients treated between 2001 and 2021. Analysis included clinical-pathological characteristics, treatment strategies, and survival. Also, we evaluated the association between RCR and survival. RESULTS: A total of 143 patients were included into our study, representing 2.9% of all early BC cases in our registry. Median age was 31 years old (range: 19-35). Most patients (93%) received endocrine therapy (ET). Of these, 18% received OFS. No survival differences were observed among treatment strategies. Median RCR score for patients treated with CT plus ET was significantly higher vs. ET alone (2.95 vs. 1.91; p = 0.0001). Conversely, patients treated with tamoxifen alone had significantly lower RCR scores vs. OFS (2.72 vs. 3.14; p = 0.04). Higher RCR scores were associated with poorer overall survival. CONCLUSION: Less than 20% of very young women with early HR + /HER2-BC in our cohort received OFS, in most cases, this involved surgical oophorectomy. RCR score was higher in patients that underwent CT and OFS and was associated with survival, regardless of treatment. We confirm the RCR score as a valuable prognostic tool to identify high-risk BC patients who could benefit from OFS.

Characterizing attitudes related to future child-bearing in young women diagnosed with early-stage breast cancer.

PURPOSE: This study characterizes attitudes and decision-making around the desire for future children in young women newly diagnosed with early-stage breast cancer and assesses how clinical factors and perceived risk may impact these attitudes. METHODS: This is a prospective study in women < 45 years with newly diagnosed stage 1-3 breast cancer. Patients completed a REDCap survey on fertility and family-building in the setting of hypothetical risk scenarios. Patient, tumor, and treatment characteristics were collected through surveys and medical record. RESULTS: Of 140 study patients [median age = 41.4 (range 23-45)], 71 (50.7%) were interested in having children. Women interested in future childbearing were younger than those who were not interested (mean = 35.2 [SD = 5.2] vs 40.9 years [3.90], respectively, p < 0.001), and more likely to be childless (81% vs 31%, p < 0.001). 54 women (77.1% of patients interested in future children) underwent/planned to undergo oocyte/embryo cryopreservation before chemotherapy. Interest in future childbearing decreased with increasing hypothetical recurrence risk, however 17% of patients wanted to have children despite a 75-100% hypothetical recurrence risk. 24.3% of patients wanted to conceive < 2 years from diagnosis, and 35% of patients with hormone receptor positive tumors were not willing to complete 5 years of hormone therapy. CONCLUSION: Many young women diagnosed with early-stage breast cancer prioritize childbearing. Interest in having a biologic child was not associated with standard prognostic risk factors. Interest decreased with increasing hypothetical recurrence risk, though some patients remained committed to future childbearing despite near certain hypothetical risk. Individual risk assessment should be included in family-planning discussions throughout the continuum of care as it can influence decision-making.

Associations between subjective social status and predictors of interest in genetic testing among women diagnosed with breast cancer at a young age.

PURPOSE: Genetic testing for gene mutations which elevate risk for breast cancer is particularly important for women diagnosed at a young age. Differences remain in access and utilization to testing across social groups, and research on the predictors of interest in genetic testing for women diagnosed at a young age is limited. METHODS: We examined the relationships between subjective social status (SSS) and variables previously identified as possible predictors of genetic testing, including genome sequencing knowledge, genetic worry, cancer worry, health consciousness, decision-making preferences, genetic self-efficacy, genetic-related beliefs, and subjective numeracy, among a cohort of women who were diagnosed with breast cancer at a young age. RESULTS: In this sample (n = 1,076), those who had higher SSS had significantly higher knowledge about the limitations of genome sequencing (Odds Ratio (OR) = 1.11; 95% CI = 1.01-1.21) and significantly higher informational norms (OR = 1.93; 95% CI = 1.19-3.14) than those with lower SSS. Similarly, education (OR = 2.75; 95% CI = 1.79-4.22), health status (OR = 2.18; 95% CI = 1.44-3.31) were significant predictors among higher SSS women compared to lower SSS women in our multivariate analysis. Lower SSS women with low self-reported income (OR = 0.13; 95% CI = 0.08-0.20) had lower odds of genetic testing interest. Our results are consistent with some prior research utilizing proxy indicators for socioeconomic status, but our research adds the importance of using a multidimensional indicator such as SSS to examine cancer and genetic testing predictor outcomes. CONCLUSION: To develop interventions to improve genetic knowledge, researchers should consider the social status and contexts of women diagnosed with breast cancer at a young age (or before 40 years old) to ensure equity in the distribution of genetic testing benefits.

Untargeted serum metabolomic profiles and breast density in young women.

PURPOSE OF THE STUDY: Breast density is an established risk factor for breast cancer. However, little is known about metabolic influences on breast density phenotypes. We conducted untargeted serum metabolomics analyses to identify metabolic signatures associated with breast density phenotypes among young women. METHODS: In a cross-sectional study of 173 young women aged 25-29 who participated in the Dietary Intervention Study in Children 2006 Follow-up Study, 449 metabolites were measured in fasting serum samples using ultra-high-performance liquid chromatography-tandem mass spectrometry. Multivariable-adjusted mixed-effects linear regression identified metabolites associated with magnetic resonance imaging measured breast density phenotypes: percent dense breast volume (%DBV), absolute dense breast volume (ADBV), and absolute non-dense breast volume (ANDBV). Metabolite results were corrected for multiple comparisons using a false discovery rate adjusted p-value (q). RESULTS: The amino acids valine and leucine were significantly inversely associated with %DBV. For each 1 SD increase in valine and leucine, %DBV decreased by 20.9% (q = 0.02) and 18.4% (q = 0.04), respectively. ANDBV was significantly positively associated with 16 lipid and one amino acid metabolites, whereas no metabolites were associated with ADBV. Metabolite set enrichment analysis also revealed associations of distinct metabolic signatures with %DBV, ADBV, and ANDBV; branched chain amino acids had the strongest inverse association with %DBV (p = 0.002); whereas, diacylglycerols and phospholipids were positively associated with ANDBV (p ≤ 0.002), no significant associations were observed for ADBV. CONCLUSION: Our results suggest an inverse association of branched chain amino acids with %DBV. Larger studies in diverse populations are needed.

Financial Toxicity Among Women with Breast Cancer Varies by Age and Race.

INTRODUCTION: Financial toxicity negatively affects clinical outcomes in breast cancer. Underrepresented demographics may be at higher risk for financial toxicity. We characterized disparities on the basis of age and other factors. PATIENTS AND METHODS: Surveys completed by women with stage 0-IV breast cancer treated at Memorial Sloan Kettering Cancer Center between 06/2022 and 05/2023 were analyzed. The comprehensive score for financial toxicity (COST) scale was used to assess financial toxicity. Descriptive statistics were calculated for differences in financial toxicity/related factors, and outcomes by age and race. Associations between variables of interest and COST scores were analyzed using linear regression. RESULTS: Of 8512 respondents (75% white, 9.3% Asian, 8.4% Black), most (68%) had clinical stage 0/I disease. Stratified by age, young Black women had higher financial toxicity than young white or Asian women (p < 0.001). On multivariable analysis, women age < 45 years experienced higher financial toxicity than older women (coefficient - 2.0, 95% CI - 2.8 to - 1.1, p < 0.001). Compared with white women, financial toxicity was greater among Black (coefficient - 6.8, 95% CI - 7.8 to - 5.8) and Asian women (coefficient - 3.5, 95% CI - 4.4 to - 2.5). Cost-related medication non-adherence was more frequent among Black and Asian women (p < 0.001). Asian women more often paid for treatment with savings than white and Black women (p < 0.001). Young women reported using savings for treatment-related costs more than older (45% vs. 32%); p < 0.001). CONCLUSIONS: Racial minorities and young patients are disproportionately affected by financial toxicity. Further studies are planned to determine how financial toxicity evolves over time and whether referral to financial services effectively reduces toxicity.

Impact of management guidelines for abnormal cervical cytology on colposcopy procedure rates among young women.

OBJECTIVE: In 2012, updated ASCCP management guidelines for abnormal cervical cytology recommended observation rather than immediate referral to colposcopy for low-grade abnormalities in women ages 21-24. We evaluated the impact of these guidelines on changes in colposcopy procedure rates among young women. METHODS: We analyzed administrative and claims data from the largest statewide family planning program between July 2011 and June 2015. Using a difference-in-differences approach, we estimated changes in colposcopy procedure rates among women ages 21-24 years before and after the 2012 ASCCP management guidelines, relative to a comparison group of women ages 25-44. RESULTS: Our analysis included 333,977 women from 216 primary care provider sites. After publication of the 2012 ASCCP management guidelines, colposcopy rates significantly declined from 6.70% (95% CI 6.21-7.19) to 3.94% (95% CI 3.60-4.29) among women ages 21-24 and from 4.35% (95% CI 4.03-4.67) to 3.53% (3.25-3.80) among women over 24 years. These declines correspond to a 1.93 percentage point reduction (95% CI 1.62-2.25; p < 0.001) in colposcopy rate among women 21-24 vs. over 24 years, or a two-fold relative reduction. Among women ages 21-24, colposcopy receipt was associated with speaking primarily English vs. non-English (OR 1.46, 95% CI 1.35-1.57), having a cervical cytology test within the past year vs. not (OR 1.55, 95% CI 1.44-1.66), and receiving care from a public vs. private provider (OR 1.31, 95% CI 1.06-1.62). CONCLUSIONS: Colposcopy procedure rates among young women significantly declined following publication of the 2012 management guidelines, which has implications for reducing potential harms of overtreatment.

Patterns of menstrual cycle, menstrual pain and medication usage in young women from high- and middle-income countries.

RESEARCH QUESTION: Do patterns of the menstrual cycle, menstrual pain and the use of medication for menstrual pain differ between young women from high-income countries (HIC) and middle-income countries (MIC)? DESIGN: A multinational, multicentre, cross-sectional study using pen-and-paper questionnaires was conducted between 2016 and 2021 to assess patterns of the menstrual cycle, menstrual pain and the use of medication for menstrual pain. Various parameters were evaluated to identify high-risk factors for severe menstrual pain in women from two HIC (n = 1550) and nine MIC (n = 7139). RESULTS: From a total of 9114 young women, 4920 medical students (HIC n = 696, MIC n = 4224) and 3769 nursing students (HIC n = 854, MIC n = 2915) were included in this study. Compared with those from HIC, a significantly higher proportion of medical and nursing students from MIC reported cyclic pain (83.9% and 86.8%, respectively) and acyclic pain (33.8% and 31.9%, respectively) (both P < 0.001). Multivariate regression analysis revealed that low body mass index and early onset of menarche were independent risk factors for severe cyclic/acyclic pain among women from HIC, and a family history of menstrual pain was a risk factor for severe cyclic/acyclic pain among women from HIC and MIC. CONCLUSIONS: Differential patterns of the menstrual cycle, menstrual pain and use of medication for menstrual pain were found between young women from HIC and MIC. A proper educational programme may be necessary for these women and healthcare providers to understand the consequences of intractable cyclic/acyclic pain, in order to facilitate early detection and timely management of menstrual pain and its negative consequences, such as endometriosis.

Psychiatric disorders and mortality due to external causes following diagnosis of endometriosis at a young age: a longitudinal register-based cohort study in Finland.

BACKGROUND: Endometriosis diagnosed in adults is associated with increased risk of various psychiatric disorders. However, little is known concerning psychiatric comorbidity and mortality due to external causes associated with endometriosis diagnosed at a young age. OBJECTIVE: This longitudinal cohort study aimed to investigate the link between surgical diagnosis of endometriosis at a young age and subsequent psychiatric disorders and mortality due to external causes. In addition, we compared the occurrence of the most common psychiatric disorders between different sites of surgically confirmed endometriosis (ovarian vs other) because of possible differences in pain manifestations. STUDY DESIGN: We conducted a retrospective register-based cohort study. Altogether 4532 women with surgically confirmed diagnosis of endometriosis before the age of 25 years from 1987 to 2012 were identified from the Finnish Hospital Discharge Register. They were matched with women without surgically diagnosed endometriosis for age and municipality on the index day (n=9014). Women were followed up from the index day until the end of 2019 for the outcomes of interest, which included 9 groups of psychiatric disorders (inpatient episodes since 1987, outpatient episodes since 1998) and death due to external causes, including deaths due to accidents, suicides, and violence (Finnish Register of Causes of Death). Cox proportional hazard models were applied to assess the crude and parity-adjusted hazard ratios and 95% confidence intervals. RESULTS: The cohort's median age was 22.9 years (interquartile range, 21.3-24.1) at the beginning and 42.5 years (36.7-48.3) after a median follow-up time of 20.0 years (14.5-25.7). We observed a higher hazard of depressive, anxiety, and bipolar disorders in women with endometriosis compared with the reference cohort, with depressive and anxiety disorders being the two most common psychiatric disorders. These differences appeared early and remained the same during the entire follow-up, irrespective of whether assessed from the data on inpatient episodes only or the data on both in- and outpatient episodes. The corresponding adjusted hazard ratios were 2.57 (95% confidence interval, 2.11-3.14) and 1.87 (1.65-2.12) for depressive disorders, 2.40 (1.81-3.17) and 2.09 (1.84-2.37) for anxiety disorders, and 1.71 (1.30-2.26) and 1.66 (1.28-2.15) for bipolar disorders, respectively. A higher hazard was observed for nonorganic sleeping disorders for the first 10 years only (3.83; 2.01-7.30) when assessed using the data on both in- and outpatient episodes. When based on inpatient records, a higher hazard for alcohol/drug dependence after 15 years of follow-up (2.07; 1.21-3.54) was observed. The difference in hazard for personality disorders tended to increase during follow-up (<10 years, 2.12 [1.28-3.52]; ≥10 years, 3.08 [1.44-6.57]). Depressive and anxiety disorders occurred more frequently in women with types of endometriosis other than ovarian endometriosis. No difference in deaths due to external causes was observed between the endometriosis and reference cohorts. CONCLUSION: Surgical diagnosis of endometriosis at a young age was associated with increased incidence of several psychiatric disorders. Moreover, within the endometriosis population, psychiatric comorbidity was more common in women with types of endometriosis other than ovarian endometriosis. We speculate that chronic pain is essential in the development of these psychiatric disorders, and that early and effective pain management is important in reducing the risk of psychiatric morbidity in young women. More research concerning the associations and management of endometriosis and associated psychiatric disorders is warranted.

Reproductive Concerns Among Young Adult Women With Breast Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: Systemic cancer treatments pose threats to fertility, leading to concerns regarding fertility and parenthood in young adult women with breast cancer (YAWBC). This systematic review aimed to synthesize existing evidence on reproductive concerns (RCs) among YAWBC and identify areas where further research in needed. METHODS: A systematic review was conducted. Nine English and Chinese databases were searched for studies from inception to June 2023. A meta-analysis was employed to pool RC levels measured using the Reproductive Concerns After Cancer scale (RCAC scale; possible total scores: 18-90). Narrative synthesis was conducted in cases where a meta-analysis could not be performed. RESULTS: Twenty-four cross-sectional studies across seven countries were included in this review. The prevalence of RCs among YAWBC ranged from 21.75% to 80%. The pooled mean total score on the overall RCAC scale was 55.84 (95% confidence interval: 53.26-58.43). "Personal health," "child's health," and "fertility potential" were the top three types of RCs among YAWBC. Sociodemographic, clinical, and psychosocial factors were found to be associated with RCs among YAWBC. Additionally, significant correlations among RCs, nonadherence to treatment, depression, and quality of life were also identified among YAWBC. CONCLUSION: RCs are a common issue among YAWBC, and age, parenthood status, fertility desire, and chemotherapy treatment are important factors associated with RCs among these women. Further research is needed to clarify RC-related factors to provide evidence aimed at tailoring interventions to mitigate RCs among YWBC.

Young Age as a Predictor of Chemotherapy Recommendation and Treatment in Breast Cancer: A National Cancer Database Study.

INTRODUCTION: Breast cancer, although the second most common malignancy in women in the United States, is rare in patients under the age of 40 y. However, this young patient population has high recurrence and mortality rates, with chemotherapy frequently used as adjuvant treatment. We aimed to determine whether age is an independent predictor of chemotherapy recommendation and subsequent treatment and the relationship to Oncotype Dx (ODX) recurrence score (RS). METHODS: The National Cancer Database was retrospectively reviewed from 2010-2016 to identify women with early-stage (pT1-pT3, pN0-pN1mic, M0), hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer who underwent ODX RS testing. RESULTS: Of 95,382 patients who met the inclusion criteria, risk groups using the traditional ODX RS cutoffs were 59% low, 33% intermediate, and 8% high. Using Trial Assigning Individualized Options for Treatment RS cutoffs, risk groups were 23% low, 62% intermediate, and 15% high. Chemotherapy recommendation decreased as age at diagnosis increased (P < 0.001). Increasing age was associated with decreased odds of chemotherapy recommendation in univariate models both continuously (odds ratio: 0.98, 95% confidence interval 0.97-0.98; P < 0.001) and categorically by decade (P < 0.001). Age by decade remained an independent prognosticator of chemotherapy recommendation (P < 0.001), adjusted for risk groups. CONCLUSIONS: Chemotherapy recommendation and treatment differs by age among patients with early-stage hormone receptor positive breast cancer who undergo ODX testing. While molecular profiling has been shown to accurately predict the benefit of chemotherapy, younger age at diagnosis is a risk factor for discordant use of ODX RS for treatment strategies in breast cancer; with patients aged 18-39 disproportionately affected.

Longitudinal analysis of the Alternative Healthy Eating Index-2010 and incident non-communicable diseases over 15 years in the 1973-1978 cohort of the Australian Longitudinal Study on Women's Health.

In studies that contain repeated measures of variables, longitudinal analysis accounting for time-varying covariates is one of the options. We aimed to explore longitudinal association between diet quality (DQ) and non-communicable diseases (NCDs). Participants from the 1973-1978 cohort of the Australian Longitudinal Study on Women's Health (ALSWH) were included, if they; responded to survey 3 (S3, 2003, aged 25-30 years) and at least one survey between survey 4 (S4, 2006) and survey 8 (S8, 2018), were free of NCDs at or before S3, and provided dietary data at S3 or S5. Outcomes were coronary heart disease (CHD), hypertension (HT), asthma, cancer (except skin cancer), diabetes mellitus (DM), depression and/or anxiety, and multimorbidity (MM). Longitudinal modelling using generalised estimation equation (GEE) approach with time-invariant (S4), time-varying (S4-S8) and lagged (S3-S7) covariates were performed. The mean (± standard deviation) of Alternative Healthy Eating Index-2010 (AHEI-2010) of participants (n = 8022) was 51·6 ± 11·0 (range: 19-91). Compared to women with the lowest DQ (AHEI-2010 quintile 1), those in quintile 5 had reduced odds of NCDs in time-invariant model (asthma: OR (95 % CI): 0·77 (0·62-0·96), time-varying model (HT: 0·71 (0·50-0·99); asthma: 0·62 (0·51-0·76); and MM: 0·75 (0·58-0·97) and lagged model (HT: 0·67 (0·49-0·91); and asthma: 0·70 (0·57-0·85). Temporal associations between diet and some NCDs were more prominent in lagged GEE analyses. Evidence of diet as NCD prevention in women aged 25-45 years is evolving, and more studies that consider different longitudinal analyses are needed.

Food Insecurity and Engagement in Transactional Sex Among Female Secondary Students in Rwanda.

The relationship between food insecurity and transactional sex is well recognized, but less is known about this relationship among adolescents. We analyzed cross-sectional baseline data from 3,130 female secondary students aged 12-19 enrolled in a three-arm, cluster randomized controlled trial to examine the association between food insecurity and transactional sex. The explanatory variable was food security and the outcome was ever engaging in transactional sex. Over one quarter (28.7%) reported any food insecurity and 1.9% of all participants (9.6% of sexually active participants) reported ever engaging in transactional sex. In adjusted models, ever experiencing any food insecurity was associated with a higher prevalence of ever transactional sex (PR: 1.60; 95% CI: 1.02, 2.49) compared to little to no food insecurity. These results provide insight into potential predictors of higher-risk sexual behavior in Rwanda; they also provide policy-makers with populations with whom to intervene on upstream determinants of transactional sex, notably poverty and food insecurity.

The Effect of Stigma on Family Planning and HIV Pre-exposure Prophylaxis Decisions of Young Women Accessing Post-Abortion Care in Kenya.

Adolescent girls and young women (AGYW) in Eastern and Southern Africa face parallel epidemics of unintended pregnancy and HIV. Their sexual health decisions are often dominated by intersecting stigmas. In an implementation science project integrating delivery of daily, oral pre-exposure prophylaxis (PrEP) for HIV prevention into 14 post-abortion care (PAC) clinics in Kenya, we enrolled a subset of PrEP initiating AGYW (aged 15 to 30 years) into a research cohort. Utilizing log binomial models, we estimated the effect of PrEP stigma on PrEP continuation (measured via self-report and urine assay for tenofovir) and abortion stigma on contraceptive initiation. Between April 2022 and February 2023, 401 AGYW were enrolled after initiating PrEP through their PAC provider, of which 120 (29.9%) initiated highly-effective contraception. Overall, abortion and PrEP stigmas were high in this cohort. Abortion stigma was more prevalent among those that were adolescents, unmarried, and reported social harm. Among 114 AGYW returning for the month 1 follow-up visit, 83.5% reported continuing PrEP and 52.5% had tenofovir detected. In this subset, higher levels of PrEP stigma were significantly associated with greater likelihood of PrEP adherence, but not PrEP continuation. For abortion stigma, greater scores in the subdomain of isolation were significantly associated with greater likelihood of initiating a highly-effective contraception, while greater scores in the subdomain of community condemnation were significantly associated with reduced likelihood of initiating a highly-effective contraception. Given the burden of stigma documented by our work, PAC settings are a pivotal space to integrate stigma-informed counseling and to empower young women to optimize contraceptive and PrEP decisions.

Applying the HIV Prevention Cascade to an Evaluation of a Large-Scale Combination HIV Prevention Programme for Adolescent Girls and Young Women in South Africa.

Adolescent girls and young women (AGYW) in South Africa are at a three times higher risk of acquiring HIV than their male counterparts. The HIV prevention cascade is a tool which can be used to measure coverage of HIV prevention services, although there is limited empirical evidence to demonstrate its application in low-resourced settings. The unifying framework is a conceptualisation of the HIV prevention cascade which theorises that both motivation and access are required for an individual to effectively use an HIV prevention method. We applied this framework to data from a random sample of 127,951 beneficiaries of a combination HIV prevention programme for AGYW aged 15-24 in South Africa to measure the steps to, and identify key barriers to, effective use of male condoms and oral pre-exposure prophylaxis (PrEP) among this vulnerable population. Barriers to each step were analysed using univariate and multivariable logistic regression. Among self-reported HIV-negative AGYW who had sex in the past 6 months, effective use of condoms (15.2%), access to PrEP (39.1%) and use of PrEP (3.8%) were low. AGYW were: less likely to be motivated to use condoms if they believed that they had a faithful partner (aOR 0.44, 95% CI 0.22-0.90) or disliked condoms (aOR 0.26, 95% CI 0.11-0.57), less likely to access condoms if the place where AGYW accessed them was far away (aOR 0.25, 95% CI 0.10-0.64), more likely to effectively use condoms if they received counselling on how to use them (aOR 2.24, 95% CI 1.05-4.76), less likely to be motivated to use PrEP if they did not believe PrEP was efficacious (aOR 0.35, 95% CI 0.17-0.72), more likely to be motivated if they felt confident that they could use PrEP, and more likely to have access to PrEP if they had ever been offered PrEP (aOR 2.94, 95% CI 1.19-7.22). This combination HIV prevention programme and similar programmes should focus on risk-reduction counselling interventions for AGYW and their male partners to improve effective use of condoms and ensure easy access to condoms and PrEP by making them available in youth-friendly spaces. Our findings demonstrate that the application of HIV prevention cascades can inform AGYW HIV prevention programming in low-resourced settings.

Factors Associated with Usage of Oral-PrEP among Female Sex Workers in Nairobi, Kenya, Assessed by Self-Report and a Point-of-Care Urine Tenofovir Immunoassay.

Pre-exposure prophylaxis (PrEP) is highly effective at reducing HIV acquisition. We aimed to estimate usage of oral-PrEP, and factors associated with adherence among female sex workers (FSWs) in Nairobi, Kenya, using a novel point-of-care urine tenofovir lateral flow assay (LFA). The Maisha Fiti study randomly selected FSWs from Sex Worker Outreach Program clinics in Nairobi. Data were collected from 1003 FSWs from June-October 2019, including surveys on self-reported oral-PrEP adherence. Adherence was also measured using the LFA for HIV-negative FSWs currently taking oral-PrEP. Informed by a social-ecological theoretical framework, we used hierarchical multivariable logistic regression models to estimate associations between individual, interpersonal/community, and structural/institutional-level factors and either self-reported or LFA-assessed adherence. Overall, 746 HIV-negative FSWs aged 18-40 participated in the study, of whom 180 (24.1%) self-reported currently taking oral-PrEP. Of these, 56 (31.1%) were adherent to oral-PrEP as measured by LFA. In the multivariable analyses, associations with currently taking oral-PrEP included having completed secondary education, high alcohol/substance use, feeling empowered to use PrEP, current intimate partner, no recent intimate partner violence, having support from sex worker organisations, experiencing sex work-related stigma, and seeking healthcare services despite stigma. Associations with oral-PrEP LFA-measured adherence measured included having only primary education, experience of childhood emotional violence, belonging to a higher wealth tertile, and being nulliparous. Oral-PrEP adherence, measured by self-report or objectively, is low among FSWs in Nairobi. Programs to improve oral-PrEP usage among FSWs should work to mitigate social and structural barriers and involve collaboration between FSWs, healthcare providers and policymakers.

Adolescent Girls and Young Women Overcoming Adherence Challenges with Vaginal and Oral PrEP Use: A Longitudinal Qualitative Study from a Crossover Trial in South Africa, Uganda, and Zimbabwe.

Rates of HIV acquisition remain high among adolescent girls and young women (AGYW) in sub-Saharan Africa. We explored South African, Ugandan, and Zimbabwean AGYW's experiences in a crossover trial of two HIV prevention products: Daily oral pre-exposure prophylaxis pills and a monthly dapivirine vaginal ring. A subset of participants (n = 25) across all sites completed up to three serial in-depth interviews (SIDIs). The SIDIs explored barriers to product use, coping strategies, and the resulting outcomes. Coded textual data were analyzed using a product acceptability conceptual framework. Participants in the SIDIs described managing the array of challenges they encountered through formal adherence support, strategic product disclosure, and personally adapted strategies. For both products, perceived discreetness of the product and decision-making around disclosure was an important component of participants' narratives. Participants tailored their coping strategies based on available personal resources (e.g., cell phone alarms for PrEP reminders, social support through disclosure) or study provided resources (e.g., encouragement from staff, adherence groups). Notably, challenges participants encountered with each product during the crossover period helped inform product selection during the choice period. Our findings suggest that-even in a context where AGYW have access to several options for HIV prevention-challenges to consistent product use remain, but accessible support mechanisms and informed choice can help mitigate these challenges. Enacting that choice may also empower AGYW to reach their short and long-term life goals-including for HIV prevention. (NCT03593655, 20th July 2018).