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PurposeBlack women have a 40% increased risk of breast cancer-related mortality. These outcome disparities may reflect differences in tumor pathways and a lack of targetable therapies for specific subtypes that are more common in Black women. Hepatocyte growth factor (HGF) is a targetable pathway that promotes breast cancer tumorigenesis, is associated with basal-like breast cancer, and is differentially expressed by race. This study assessed whether a 38-gene HGF expression signature is associated with recurrence and survival in Black and non-Black women.MethodsStudy participants included 1957 invasive breast cancer cases from the Carolina Breast Cancer Study. The HGF signature was evaluated in association with recurrence (n = 1251, 171 recurrences), overall, and breast cancer-specific mortality (n = 706, 190/328 breast cancer/overall deaths) using Cox proportional hazard models.ResultsWomen with HGF-positive tumors had higher recurrence rates [HR 1.88, 95% CI (1.19, 2.98)], breast cancer-specific mortality [HR 1.90, 95% CI (1.26, 2.85)], and overall mortality [HR 1.69; 95% CI (1.17, 2.43)]. Among Black women, HGF positivity was significantly associated with higher 5-year rate of recurrence [HR 1.73; 95% CI (1.01, 2.99)], but this association was not significant in non-Black women [HR 1.68; 95% CI (0.72, 3.90)]. Among Black women, HGF-positive tumors had elevated breast cancer-specific mortality [HR 1.80, 95% CI (1.05, 3.09)], which was not significant in non-Black women [HR 1.52; 95% CI (0.78, 2.99)].ConclusionThis multi-gene HGF signature is a poor-prognosis feature for breast cancer and may identify patients who could benefit from HGF-targeted treatments, an unmet need for Black and triple-negative patients.

Simple Summary: Adolescents and young adults (AYAs) experiencing cancer have support needs that differ from older adult cancer patients. The aim of our qualitative study was to determine the holistic needs of AYA cancer survivors and to develop a patient-centered conceptual model of AYA survivorship care. Analysis of our interview results reveals eight key domains critical to holistic patient-centered AYA survivorship care. We offer a conceptual model that differs from current conceptual models of AYA survivorship care by centering the patient and their support systems, emphasizing the need for continuing supportive navigation, and the importance of repeated support along the identified domains over time. Purpose: Conceptual models provide frameworks to illustrate relationships among patient-, provider-, system-, and community-level factors that inform care delivery and research. Existing models of cancer survivorship care focus largely on pediatric or adult populations whose needs differ from adolescents and young adults (AYAs). We developed a patient-centered conceptual model of AYA survivorship care. Methods: We conducted a narrative literature review of current conceptual and theoretical models of care. We engaged AYA cancer survivors (n = 25) in semi-structured one-hour telephone interviews. Most participants were in their 20s and 30s, and the majority (84%) were women. Recruitment was stratified by age and time since cancer diagnosis. We conducted a thematic analysis of interview transcripts to identify themes that exemplified patient-centered care. Results: Most participants identified as white and female. Leukemia and breast cancer were the most common cancer types. Main themes included the need for (1) care coordination, (2) ongoing mental health support, (3) connection to AYA peer support, (4) support during fertility preservation efforts, (5) support with financial burden, (6) support for quality of life, (7) information about and support with side effects and late effects, and (8) attention to the unique needs of young adults. Conclusions: We present a patient-centered conceptual model of AYA survivorship care needs that can inform future cancer care delivery and research. [ABSTRACT FROM AUTHOR]

Background Many women diagnosed with cancer as adolescents and young adults (AYAs, age 15-39 years) want biological children after cancer but lack information on the potential impact of their cancer history on future reproductive outcomes. We investigated the risk of adverse birth outcomes among AYA cancer survivors. Methods We identified insured women diagnosed with AYA breast cancer, thyroid cancer, gynecologic cancers, lymphoma, or melanoma from 2003 to 2016 in the state of North Carolina or the Kaiser Permanente health care systems in northern and southern California. Post-diagnosis births to cancer survivors were each matched with up to 5 births to women without cancer. Risk ratios for preterm birth (<37 completed weeks), very preterm birth (<34 completed weeks), low birth weight (<2500 g), and small for gestational age (SGA, <10th percentile of weight for gestational age) were estimated using modified Poisson regression. Results Analyses included 1648 births to 1268 AYA cancer survivors and 7879 births to 6066 women without cancer. Overall, risk of preterm birth, very preterm birth, low birth weight, and SGA did not significantly differ between births to women with and without cancer. However, births to women with gynecologic cancers had a significantly increased risk of low birth weight (risk ratio = 1.82; 95% confidence interval: 1.03 to 3.21) and suggested increased risk of preterm birth (risk ratio = 1.59; 95% confidence interval: 0.99 to 2.54). Chemotherapy exposure was not associated with increased risk of adverse birth outcomes. Conclusions Women with gynecologic cancers, but not other cancers, had an increased risk of adverse birth outcomes compared to women without cancer. [ABSTRACT FROM AUTHOR]

Study Question: What are the associations between a history of cancer and outcomes after ART?Summary Answer: Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer and a lower likelihood of clinical pregnancy and live birth after ART.What Is Known Already: Small, single-institution studies have suggested that cancer and its treatment may negatively affect ART outcomes.Study Design, Size, Duration: We conducted a systematic review with meta-analysis of studies comparing ART outcomes between women with and without cancer. PubMed, Embase and Scopus were searched for original, English-language studies published up to June 2021.Participants/materials, Setting, Methods: Inclusion criteria required reporting of ART outcomes after controlled ovarian stimulation (COS) among women with a history of cancer compared to women without cancer who used ART for any indication. Outcomes of interest ranged from duration of COS to likelihood of live birth after embryo transfer. Random-effects meta-analysis was used to calculate mean differences and odds ratios (ORs) with 95% CIs and 95% prediction intervals (PIs). We assessed heterogeneity by age-adjustment, referent group indication for ART, study location and among women with breast cancer and women who initiated ART before cancer treatment. We used visual inspection, Egger's test and the trim-and-fill method to assess funnel plot asymmetry.Main Results and the Role Of Chance: Of 6094 unique records identified, 42 studies met inclusion criteria, representing a median per study of 58 women with cancer (interquartile range (IQR) = 159) and 114 women without cancer (IQR = 348). Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer (OR: 0.22; 95% CI: 0.07, 0.74; 95% PI: 0.00, 64.98); lower likelihood of clinical pregnancy (OR: 0.51; 95% CI: 0.35, 0.73; 95% PI: 0.19, 1.35); and lower likelihood of live birth (OR: 0.56; 95% CI: 0.38, 0.83; 95% PI: 0.19, 1.69). Substantial among-study heterogeneity was observed for COS duration, gonadotropin dose, cycle cancellation, total oocytes and mature oocytes. Fertilization percentage showed less heterogeneity, but study-specific estimates were imprecise. Similarly, number of embryos showed less heterogeneity, and most studies estimated minimal differences by cancer history. Funnel plot asymmetry was observed for estradiol peak and oocyte maturation percentage.Limitations, Reasons For Caution: Appreciable confounding is possible in 11 studies that lacked adequate control for group differences in age, and among-study heterogeneity was observed for most outcomes. Lack of data limited our ability to assess how cancer clinical factors (e.g. cancers other than breast, cancer stage and treatment) and ART cycle characteristics (e.g. fresh versus frozen embryo transfers and use of gestational carriers) may affect outcomes.Wider Implications Of the Findings: Women with cancer may be less likely to achieve pregnancy and live birth after embryo transfer. Further examination of reproductive outcomes and sources of heterogeneity among studies is warranted to improve evidence of the expected success of ART after a cancer diagnosis.Study Funding/competing Interest(s): This research was supported in part by R01 CA211093 and P30 ES010126. C.M. was supported by the University of North Carolina Lineberger Cancer Control Education Program (T32 CA057726) and the National Cancer Institute (F31 CA260787). J.A.R.-H. was supported by the National Cancer Institute (K08 CA234333, P30 CA016672). J.A.R.-H. reports receiving consulting fees from Schlesinger Group and Guidepoint. The remaining authors declare no competing interests.Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Blood-based biomarkers for gastric cancer risk stratification could facilitate targeting screening to people who will benefit from it most. The ABC Method, which stratifies individuals by their Helicobacter pylori infection and serum-diagnosed chronic atrophic gastritis status, is currently used in Japan for this purpose. Most gastric cancers are caused by chronic H. pylori infection, but few studies have explored the capability of antibody response to H. pylori proteins to predict gastric cancer risk in addition to established predictors. Methods: We used the least absolute shrinkage and selection operator (Lasso) to build a predictive model of noncardia gastric adenocarcinoma risk from serum data on pepsinogen and antibody response to 13 H. pylori antigens as well as demographic and lifestyle factors from a large international study in East Asia. Results: Our best model had a significantly (P < 0.001) higher AUC of 73.79% [95% confidence interval (CI), 70.86%-76.73%] than the ABC Method (68.75%; 95% CI, 65.91%-71.58%). At 75% specificity, the new model had greater sensitivity than the ABC Method (58.67% vs. 52.68%) as well as NPV (68.24% vs. 66.29%). Conclusions: Along with serologically defined chronic atrophic gastritis, antibody response to the H. pylori proteins HP 0305, HP 1564, and UreA can improve the prediction of gastric cancer risk. Impact: The new risk stratification model could help target more invasive gastric screening resources to individuals at high risk. [ABSTRACT FROM AUTHOR]

Background: Breast cancers in recently postpartum women may have worse outcomes, but studies examining tumor molecular features by pregnancy recency have shown conflicting results. Methods: This analysis used Carolina Breast Cancer Study data to examine clinical and molecular tumor features among women less than 50 years of age who were recently (=10 years prior) or remotely (>10 years prior) postpartum, or nulliparous. Prevalence odds ratios (POR) and 95% confidence intervals (CI) were estimated using multivariable models. Results: Recently postpartum women (N = 618) were more frequently lymph node-positive [POR (95% CI): 1.66 (1.26-2.19)], estrogen receptor (ER)-negative [1.37 (1.02-1.83)], and IHC-based triple negative [1.57 (1.00-2.47)] compared with nulliparous (N = 360) women. Some differences were identified between recent versus remotely postpartum; smaller tumor size [0.67 (0.52-0.86)], p53 wildtype [0.53 (0.36-0.77)], and non-basal-like phenotype [0.53 (0.33-0.84)] were more common among recently postpartum. Recently postpartum (vs. nulliparous) had significant enrichment for adaptive immunity, T cells, B cells, CD8 T cells, activated CD8 T cells/natural killer (NK) cells, and T follicular helper (Tfh) cells and higher overall immune cell scores. These differences were attenuated in remotely (compared with recently) postpartum women. Conclusions: These results suggest a dominant effect of parity (vs. nulliparity) and a lesser effect of pregnancy recency on tumor molecular features, although tumor immune microenvironments were altered in association with pregnancy recency. [ABSTRACT FROM AUTHOR]