The Risk Factors, Incidence and Prognosis of Postpartum Breast Cancer: A Nationwide Study by the SMARTSHIP Group

Park, Sung Min; Lee, Ji Sung; Yoon, Jong‐Hwan; Kim, Nam Hyoung; Park, Seho; Youn, Hyun Jo; Lee, Jong Won; Lee, Jung Eun; Lee, Jihyoun; Hur, Ho; Jeong, Jong Ju; Kim, Kweon-Cheon; Bae, Soo Youn

doi:10.3389/fonc.2022.889433

Cited by 6 publications

(11 citation statements)

References 53 publications

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“…These data are consistent with prior studies identifying a postpartum diagnosis as an independent risk factor for breast cancer metastases, breast cancer specific death, and overall mortality, across diverse, breast cancer populations 22,23,26–30 . Further, results of this study expand the understanding of PPBC by demonstrating increased risk for mortality in germline BRCA PV carriers diagnosed with PPBC.…”

Section: Discussionsupporting

confidence: 91%

A Postpartum Breast Cancer Diagnosis Reduces Survival in GermlineBRCApathogenic variant Carriers

Zhang,

Ye,

Bernhardt

et al. 2023

Preprint

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IMPORTANCEIn young-onset breast cancer, a diagnosis within 5-10 years of childbirth associates with increased mortality. Women with germlineBRCA1/2pathogenic variants (PVs) are more likely to be diagnosed with breast cancer at younger ages, but the impact of childbirth on mortality is unknown.OBJECTIVEDetermine whether time between recent childbirth and breast cancer diagnosis impacts mortality among young-onset breast cancer patients with germlineBRCA1/2PVs.DESIGN, SETTING, AND PARTICIPANTSThis prospective cohort study includes 903 women with germlineBRCA1/2PVs diagnosed with stage I-III breast cancer at ≤45 years of age, between 1950-2021 in the UK.MAIN OUTCOMES AND MEASURESThe primary outcome is all-cause mortality, censored at 20 years post-diagnosis. The primary exposure is time between most recent childbirth and breast cancer diagnosis, with recent childbirth defined as >0-<10 years post childbirth (n=419)], further delineated to >0-<5 years (n=228) and 5-<10 years (n=191). Mortality of nulliparous cases (n=224) was compared to the recent postpartum groups and the ≥10 years postpartum (n=260) group. Cox proportional hazards regression analyses were adjusted for patient age, tumor stage, further stratified by tumor estrogen receptor (ER) andBRCAgene status.RESULTSFor allBRCAPV carriers, increased all-cause mortality was observed in women diagnosed >0-<10 years postpartum, compared to nulliparous and ≥10 years groups, demonstrating the transient duration of postpartum risk. Risk of mortality was greater for ER-positive cases in the >0-<5 group [HR=2.35 (95% CI, 1.02-5.42)] and ER-negative cases in the 5-<10 group [HR=3.12 (95% CI, 1.22-7.97)] compared to the nulliparous group. Delineated byBRCA1orBRCA2, mortality in the 5-<10 group was significantly increased, but only forBRCA1carriers [HR=2.03 (95% CI, 1.15-3.58)].CONCLUSIONS AND RELEVANCEYoung-onset breast cancer with germlineBRCAPVs confers increased risk for all-cause mortality if diagnosed within 10 years of childbirth, with risk highest for ER+ cases at >0-<5 years postpartum, and for ER-cases at 5-<10 years postpartum.BRCA1carriers are at highest risk for poor prognosis when diagnosed at 5-10 years postpartum. No such associations were observed forBRCA2carriers. These results should inform genetic counseling, prevention, and treatment strategies forBRCAPV carriers.Key PointsQuestionIs a postpartum diagnosis an independent risk factor for mortality among young-onset breast cancer patients with germlineBRCA1/2PVs?FindingsA diagnosis <10 years postpartum associates with higher risk of mortality compared to nulliparous and ≥10 years postpartum cases. Peak risk after childbirth varies for ER-positive (>0-<5 years) vs. ER-negative cases (5-<10 years).BRCA1carriers had peak risk of mortality 5-10 years postpartum, with no associations observed forBRCA2carriers.MeaningA breast cancer diagnosis within 10 years of childbirth independently associates with increased risk for mortality in patients with germlineBRCA1/2PVs, especially for carriers ofBRCA1PVs.

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Section: Discussionsupporting

confidence: 91%

A Postpartum Breast Cancer Diagnosis Reduces Survival in GermlineBRCApathogenic variant Carriers

Zhang,

Ye,

Bernhardt

et al. 2023

Preprint

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“…While numerous studies have examined reproductive risk factors that influence BRCA1/2 BC rates with the goal of reducing incidence, here we assessed reproductive factors associated with survival. 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 . Furthermore, results of this study expand the understanding of PPBC by demonstrating increased risk for mortality in germline BRCA PV carriers diagnosed with PPBC.…”

Section: Discussionsupporting

confidence: 90%

“…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: 88%

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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“…Breast cancers diagnosed during pregnancy and up to one year postpartum are generally more aggressive tumors characterized by unfavorable clinicopathological fatures such as high tumor grade, low level of expression of estrogen and progesterone receptors in comparison to those breast cancers diagnosed in nongravid women of the same age (Tretli et al 1988;Basaran et al 2014;Iqbal et al 2017). But the impact of pregnancy on the survival remains a matter of debate (Azim et al 2012;Amant et al 2013;Hartman and Eslick 2016;Iqbal et al 2017;Jerzak et al 2021;Park et al 2022).…”

Section: Pregnancy In Breast Cancermentioning

confidence: 99%

Breast cancer treatment and ovarian function

Yıldız

Bildik²,

Benlioğlu³

et al. 2023

Reproductive BioMedicine Online

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The Risk Factors, Incidence and Prognosis of Postpartum Breast Cancer: A Nationwide Study by the SMARTSHIP Group

Cited by 6 publications

References 53 publications

A Postpartum Breast Cancer Diagnosis Reduces Survival in GermlineBRCApathogenic variant Carriers

A Postpartum Breast Cancer Diagnosis Reduces Survival in GermlineBRCApathogenic variant Carriers

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

Breast cancer treatment and ovarian function

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