Young-Onset Breast Cancer Outcomes by Time Since Recent Childbirth in Utah

Zhang, Zhenzhen; Bassale, Solange; Jindal, Sonali; Fraser, Alison; Guinto, Emily; Anderson, Weston; Mori, Motomi; Smith, Ken R.; Schedin, Pepper

doi:10.1001/jamanetworkopen.2022.36763

Cited by 14 publications

(25 citation statements)

References 67 publications

(152 reference statements)

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“…As these changes are more pronounced during the early postpartum period, we examined the changes in the biological pathways altered in early PPBC in comparison those which occurred late PPBC. In line with other large cohort studies (34,35), our ndings show increased risk of metastasis in BC patients within 1-5 years of postpartum duration. Early menarche and older age at rst and last childbirth were observed in early PPBC tumors compared to other groups.…”

Section: Discussionsupporting

confidence: 92%

Premenopausal women with breast cancer in the early postpartum period show molecular profiles of invasion and are associated with poor prognosis

Prabhu

Nimbalkar

Snijesh

et al. 2023

Preprint

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Background Though pregnancy and lactation are considered as protective factors against development of breast cancer (BC), small proportion of young premenopausal women develop tumors within 5 to 10 years of last childbirth presenting with aggressive disease. The exact mechanisms that lead to poor prognosis in these postpartum breast cancers (PPBC) is largely unknown. Methods We have evaluated the association of clinical and reproductive factors with BC in a cohort of women ≤ 45 years (N = 155) with long term follow up. Based on duration since last childbirth (LCB), they were grouped into PPBC1 (LCB ≤ 5 years), PPBC2 (LCB between 6–10 years), PPBC3 (LCB > 10 years) and NPBC (age matched nulliparous BC patients). Disease free survival and hazard associated with recurrence/metastasis were compared between the groups. RNA sequencing of tumor samples from three different parous groups (n = 10) was performed and transcriptomic data was analyzed for differentially expressed genes and altered pathways. Results Women in the PPBC1 group had an early menarche and late first and last childbirth compared to other groups. Survival analysis within lymph node positive tumors showed that PPBC1 tumors had a worse prognosis compared to PPBC2 and NPBC tumors (p = 0.015, and p = 0.026 respectively with a higher hazard both by univariate and multivariate analysis). Clustering of the differentially expressed genes between the groups showed distinct expression in early PPBC (PPBC1) tumors. Pathway analysis revealed upregulation of invasive signature along with T cell exhaustion, extracellular matrix remodeling, angiogenesis and epithelial to mesenchymal transition within early PPBC tumors. Conclusion PPBC diagnosis may represent a unique subtype of cancer that requires distinct clinical and translational research to understand altered pathways. Clinical parameters and biologic subtyping alone may be insufficient to accurately project the risk of recurrence and optimal treatment strategies in young patients who develop BC in the early postpartum period.

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Section: Discussionsupporting

confidence: 92%

Premenopausal women with breast cancer in the early postpartum period show molecular profiles of invasion and are associated with poor prognosis

Prabhu

Nimbalkar

Snijesh

et al. 2023

Preprint

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“…Our data are consistent with prior studies identifying a PPBC diagnosis as an independent risk factor associated with BC metastases, BC-specific death, and overall mortality across diverse BC populations. 22,23,[26][27][28][29][30] Furthermore, results of this study expand the understanding of PPBC by demonstrating increased risk for mortality in germline BRCA PV carriers diagnosed with PPBC. This study has implications for standard of care for women with BRCA1/2 YOBC, as well as for genetic counseling of germline BRCA1/2 PV carriers.…”

Section: Discussionmentioning

confidence: 93%

“…Analyses were performed on the 3 groups (nulliparous, PPBC 0 to <10 years, and ≥10 years since recent childbirth). Also, where sample sizes permitted, we further delineated the PPBC group into 0 to less than 5 years and 5 to less than 10 years subgroups, as some studies have reported that closer proximity to recent childbirth was associated with worse prognosis …”

Section: Methodsmentioning

confidence: 99%

“…11 Importantly, compared with later age-onset BC, YOBC is enriched with poor prognostic tumor features [12][13][14][15][16] and is associated with higher mortality 6,11,15,17,18 An emerging body of work suggest that the postpartum period is a high-risk window for initiation of new cancers and the rapid progression of subclinical lesions to cancers with metastatic phenotypes. [19][20][21][22][23] Meta-analyses of YOBC showed a postpartum diagnosis up to 10 years after childbirth was consistently associated with increased risk of distant metastasis and death. 19,20,24 These BCs are defined as postpartum BC (PPBC).…”

Section: Introductionmentioning

confidence: 99%

“…An emerging body of work suggest that the postpartum period is a high-risk window for initiation of new cancers and the rapid progression of subclinical lesions to cancers with metastatic phenotypes . Meta-analyses of YOBC showed a postpartum diagnosis up to 10 years after childbirth was consistently associated with increased risk of distant metastasis and death .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Postpartum Breast Cancer and Survival in Women With Germline BRCA Pathogenic Variants

Zhang,

Ye,

Bernhardt

et al. 2024

JAMA Netw Open

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ImportanceIn young-onset breast cancer (YOBC), a diagnosis within 5 to 10 years of childbirth is associated with increased mortality. Women with germline BRCA1/2 pathogenic variants (PVs) are more likely to be diagnosed with BC at younger ages, but the impact of childbirth on mortality is unknown.ObjectiveTo determine whether time between most recent childbirth and BC diagnosis is associated with mortality among patients with YOBC and germline BRCA1/2 PVs.Design, Setting, and ParticipantsThis prospective cohort study included women with germline BRCA1/2 PVs diagnosed with stage I to III BC at age 45 years or younger between 1950 and 2021 in the United Kingdom, who were followed up until November 2021. Data were analyzed from December 3, 2021, to November 29, 2023.ExposureTime between most recent childbirth and subsequent BC diagnosis, with recent childbirth defined as 0 to less than 10 years, further delineated to 0 to less than 5 years and 5 to less than 10 years.Main Outcomes and MeasuresThe primary outcome was all-cause mortality, censored at 20 years after YOBC diagnosis. Mortality of nulliparous women was compared with the recent post partum groups and the 10 or more years post partum group. Cox proportional hazards regression analyses were adjusted for age, tumor stage, and further stratified by tumor estrogen receptor (ER) and BRCA gene status.ResultsAmong 903 women with BRCA PVs (mean [SD] age at diagnosis, 34.7 [6.1] years; mean [SD] follow-up, 10.8 [9.8] years), 419 received a BC diagnosis 0 to less than 10 years after childbirth, including 228 women diagnosed less than 5 years after childbirth and 191 women diagnosed 5 to less than 10 years after childbirth. Increased all-cause mortality was observed in women diagnosed within 5 to less than 10 years post partum (hazard ratio [HR], 1.56 [95% CI, 1.05-2.30]) compared with nulliparous women and women diagnosed 10 or more years after childbirth, suggesting a transient duration of postpartum risk. Risk of mortality was greater for women with ER-positive BC in the less than 5 years post partum group (HR, 2.35 [95% CI, 1.02-5.42]) and ER-negative BC in the 5 to less than 10 years post partum group (HR, 3.12 [95% CI, 1.22-7.97]) compared with the nulliparous group. Delineated by BRCA1 or BRCA2, mortality in the 5 to less than 10 years post partum group was significantly increased, but only for BRCA1 carriers (HR, 2.03 [95% CI, 1.15-3.58]).Conclusions and RelevanceThese findings suggest that YOBC with germline BRCA PVs was associated with increased risk for all-cause mortality if diagnosed within 10 years after last childbirth, with risk highest for ER-positive BC diagnosed less than 5 years post partum, and for ER-negative BC diagnosed 5 to less than 10 years post partum. BRCA1 carriers were at highest risk for poor prognosis when diagnosed at 5 to less than 10 years post partum. No such associations were observed for BRCA2 carriers. These results should inform genetic counseling, prevention, and treatment strategies for BRCA PV carriers.

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Premenopausal women with breast cancer in the early post-partum period show molecular profiles of invasion and are associated with poor prognosis

Nimbalkar

Snijesh

Rajarajan

et al. 2023

Breast Cancer Res Treat

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Purpose Young premenopausal women develop breast cancer (BC) within 5–10 years of the last childbirth, known as post-partum breast cancers (PPBC), often present with aggressive disease. The exact mechanisms that lead to poor prognosis in these patients are largely unknown. Methods We have evaluated the association of clinical and reproductive factors with BC in a cohort of women ≤ 45 years (N = 155) with long-term follow-up. Based on duration since last childbirth (LCB), grouped patients into PPBC1 (LCB ≤ 5 years), PPBC2 (LCB between 6 and 10 years), PPBC3 (LCB > 10 years), and NPBC (age-matched nulliparous BC patients). We compared disease-free survival and hazard associated with recurrence/metastasis between the groups. RNA sequencing of tumor samples was performed from three parous groups (n = 10), and transcriptomic data were analyzed for differentially expressed genes and altered pathways. Results Women in the PPBC1 group had an early menarche and late age at first and last childbirth compared to other groups. Survival analysis within lymph node-positive tumors showed that PPBC1 tumors had a worse prognosis than PPBC2 and NPBC tumors (p = 0.015 and p = 0.026, respectively). Clustering of the differentially expressed genes between the groups showed distinct expression in early PPBC (E-PPBC) tumors. Pathway analysis revealed upregulation of invasive-related pathways along with T cell exhaustion, extracellular matrix remodeling, angiogenesis, and epithelial-to-mesenchymal transition in E-PPBC tumors. Conclusion Early PPBC is a unique subtype with aggressive clinical features and distinct biology. Further research is needed to accurately project the risk of recurrence and optimal treatment strategies in these young patients.

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Young-Onset Breast Cancer Outcomes by Time Since Recent Childbirth in Utah

Cited by 14 publications

References 67 publications

Premenopausal women with breast cancer in the early postpartum period show molecular profiles of invasion and are associated with poor prognosis

Premenopausal women with breast cancer in the early postpartum period show molecular profiles of invasion and are associated with poor prognosis

Postpartum Breast Cancer and Survival in Women With Germline BRCA Pathogenic Variants

Premenopausal women with breast cancer in the early post-partum period show molecular profiles of invasion and are associated with poor prognosis

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