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Postpartum diagnosis demonstrates a high risk for metastasis and merits an expanded definition of pregnancy-associated breast cancer.

ABSTRACT: Previous studies report conflicting data on outcomes of pregnancy-associated breast cancer (PABC). Our aim was to examine the effect of a postpartum diagnosis on maternal prognosis in a young women's breast cancer cohort. We conducted a retrospective cohort study of women age ≤45 years, diagnosed with breast cancer (n = 619) during 1981-2011 at the University of Colorado Hospital and The Shaw Cancer Center in Edwards, CO. Breast cancer cases were grouped according to time between giving birth and diagnosis: nulliparous (n = 125), pregnant (n = 24), < 5 years postpartum (n = 136), >5-<10 postpartum (n = 130), and ≥10 years postpartum (n = 147), to examine the clinicopathologic features and the risk of distance recurrence and death. Cases diagnosed after pregnancy, but within five-years postpartum, had an approximate three fold increased risk of distant recurrence (HR 2.80, 95 % CI: 1.12-6.57) and death (HR 2.65, 95 % CI: 1.09-6.42) compared to nulliparous cases. Postpartum cases diagnosed within five years of last childbirth demonstrated a higher five-year distant recurrence probability (31.1 %) and a markedly lower five-year overall survival probability (65.8 %) compared to nulliparous cases (14.8 and 98.0 %, respectively). A diagnosis of breast cancer during the first five-years postpartum confers poorer maternal prognoses after adjustment for biologic subtype, stage, and year of diagnosis. We propose that the definition of PABC should include cases diagnosed up to at least five-years postpartum to better delineate the increased risk imparted by a postpartum diagnosis. Based on emerging preclinical and epidemiologic data, we propose that pregnant and postpartum cases be researched as distinct subsets of PABC to clarify the risk imparted by pregnancy and the events subsequent to pregnancy, such as breast involution, on breast cancer. Further, we highlight the importance of postpartum breast cancer as an area for further research to reduce the increased metastatic potential and mortality of PABC.

SUBMITTER: Callihan EB

PROVIDER: S-EPMC3608871 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceIn women 45 years or younger, breast cancer diagnosis after childbirth increases the risk for metastasis and death, yet limited data exist to define this window of risk and associated prognostic factors.ObjectiveTo assess the window of elevated risk for metastasis following a postpartum breast cancer (PPBC) diagnosis and whether clinical prognostic factors are associated with the increased risk.Design, setting, and participantsThis multicenter cohort study conducted using cases from the Colorado Young Women's Breast Cancer Cohort diagnosed between January 1, 1981, and December 31, 2014, included 701 women 45 years or younger with stage I to III invasive breast cancer for whom parity data, including time of last childbirth, were available. Data analysis was conducted from July 1 to September 30, 2017. This study involved a tertiary care academic hospital-based breast center and its regional affiliates with cases from the greater Rocky Mountain region.ExposuresPrimary exposures were prior childbirth or no childbirth, time between most recent childbirth and breast cancer diagnosis, and time between breast cancer diagnosis and metastasis.Main outcomes and measuresThe primary outcome was distant metastasis-free survival.ResultsA total of 701 women 45 years or younger from the greater Rocky Mountain states region were included in the analysis; mean (SD) age at diagnosis was 37.9 (5.1) years. Breast cancer diagnosis within 10 years after parturition was associated with elevated risk for metastasis, particularly in women with stage I or II disease. In addition, women with PPBC diagnosed within 10 years of a completed pregnancy that was estrogen receptor-positive showed distant metastasis-free survival similar to that of nulliparous patients with estrogen receptor-negative cancer, and women with estrogen receptor-negative PPBC had further reduced metastasis-free survival. Moreover, women with PPBC had increased lymphovascular invasion and lymph node involvement. In addition, tumor-associated Ki67 positivity identified 129 patients with luminal B cancer in the cohort that, independent of parity status, had poorer prognosis compared with patients with luminal A cancer, although it did not reach statistical significance.Conclusions and relevanceDiagnosis of PPBC within 10 years post partum appears to be associated with an increased risk for metastasis. This increased risk was highest in stages I and II cancer at diagnosis and present in both patients with estrogen receptor-positive and estrogen receptor-negative cancer, persisting in estrogen receptor-positive cases for up to 15 years after diagnosis. Postpartum breast cancer diagnoses were not associated with increased Ki67 index but were associated with increased lymphovascular invasion and lymph node involvement compared with breast cancer in nulliparous patients.

Project description:BackgroundLow specificity in current breast imaging modalities leads to increased unnecessary follow-ups and biopsies. The purpose of this study is to evaluate the efficacy of combining the quantitative parameters of high-definition microvasculature imaging (HDMI) and 2D shear wave elastography (SWE) with clinical factors (lesion depth and age) for improving breast lesion differentiation.MethodsIn this prospective study, from June 2016 through April 2021, patients with breast lesions identified on diagnostic ultrasound and recommended for core needle biopsy were recruited. HDMI and SWE were conducted prior to biopsies. Two new HDMI parameters, Murray's deviation and bifurcation angle, and a new SWE parameter, mass characteristic frequency, were included for quantitative analysis. Lesion malignancy prediction models based on HDMI only, SWE only, the combination of HDMI and SWE, and the combination of HDMI, SWE and clinical factors were trained via elastic net logistic regression with 70% (360/514) randomly selected data and validated with the remaining 30% (154/514) data. Prediction performances in the validation test set were compared across models with respect to area under the ROC curve as well as sensitivity and specificity based on optimized threshold selection.ResultsA total of 508 participants (mean age, 54 years ± 15), including 507 female participants and 1 male participant, with 514 suspicious breast lesions (range, 4-72 mm, median size, 13 mm) were included. Of the lesions, 204 were malignant. The SWE-HDMI prediction model, combining quantitative parameters from SWE and HDMI, with AUC of 0.973 (95% CI 0.95-0.99), was significantly higher than the result predicted with the SWE model or HDMI model alone. With an optimal cutoff of 0.25 for the malignancy probability, the sensitivity and specificity were 95.5% and 89.7%, respectively. The specificity was further improved with the addition of clinical factors. The corresponding model defined as the SWE-HDMI-C prediction model had an AUC of 0.981 (95% CI 0.96-1.00).ConclusionsThe SWE-HDMI-C detection model, a combination of SWE estimates, HDMI quantitative biomarkers and clinical factors, greatly improved the accuracy in breast lesion characterization.

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Postpartum diagnosis demonstrates a high risk for metastasis and merits an expanded definition of pregnancy-associated breast cancer.

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