Elsevier

Cancer Treatment Reviews

Volume 38, Issue 7, November 2012, Pages 834-842
Cancer Treatment Reviews

Controversy
Prognosis of pregnancy-associated breast cancer: A meta-analysis of 30 studies

https://doi.org/10.1016/j.ctrv.2012.06.004Get rights and content

Abstract

Background

Pregnancy-associated breast cancer (PABC) is relatively rare with considerable controversy regarding its prognosis.

Patients & methods

Two of the authors independently performed a literature search with no date or language restrictions. Eligible studies were control-matched, population-based and hospital-based studies that addressed the outcome of patients diagnosed during pregnancy or 1-year afterwards. The primary and secondary end-points were overall and disease-free survival respectively. Pooling of data was done using the random effect model.

Results

30 studies were included in this meta-analysis (3,628 cases and 37,100 controls). PABC patients had a significantly higher risk of death compared to those with non-pregnancy-related breast cancer (pooled hazard ratio (pHR): 1.44; 95% CI [1.27–1.63]). The same results were encountered on restricting the analysis to HRs of multivariate analyses (pHR: 1.40 [1.17–1.67]). A clearer trend of poorer outcome was seen in those diagnosed postpartum (pHR: 1.84; 95% CI [1.28–2.65]) than those diagnosed during pregnancy (pHR: 1.29; 95% CI [0.74–2.24]). DFS analysis showed a significantly higher risk of relapse associated with PABC as well (pHR: 1.60 [1.19–2.16]).

Conclusion

Our results show that PABC is independently associated with poor survival particularly those diagnosed shortly post-partum. This underscores a possible impact of the pregnant breast microenvironment on the biology and consequently the prognosis of these tumors.

Introduction

Pregnancy-associated breast cancer (PABC) is commonly defined as breast cancer diagnosed during the course of pregnancy or the one-year following delivery.1 The exact incidence is unknown; however, it is estimated to constitute around 10% of breast cancer cases diagnosed below the age of 40 in Western nations.2, 3 This incidence is currently on the rise as more women are delaying childbearing.4

Prognosis of PABC has been addressed in several studies with inconsistent results.5, 6, 7, 8 The relative rarity of the disease precludes the conduction of large powered controlled studies to address this question. Some studies have found that PABC is more commonly diagnosed at an advanced stage5, 6 suggesting that the poor prognosis is secondary to diagnostic delay rather than an inherent effect of pregnancy or lactation on breast cancer prognosis. However, other studies have shown an independent effect of pregnancy on outcome.9, 10, 11 Nevertheless, the small number of patients examined in each of the individual studies has hindered the proper interpretation of these data. This is of great clinical relevance as it could guide treatment strategies for these highly challenging cases.

In this study, we aimed to perform a comprehensive analysis of all published studies that addressed the prognosis of PABC. We specifically wanted to clarify whether diagnosis during pregnancy or 1-year afterwards has an impact on long-term patient outcome.

Section snippets

Methods

The study design was a quantitative synthesis of retrospective control-matched, population-based and hospital-based studies that evaluated the impact of breast cancer diagnosis during or one year following pregnancy on survival. The primary end-point was overall survival (OS), which was defined as time from breast cancer diagnosis to death or last follow-up. Secondary end-points included disease-free survival (DFS), defined as time from breast cancer diagnosis to local or systemic relapse,

Eligible studies

A total of 6449 articles were initially screened. After applying eligibility criteria, a total of 30 studies were deemed to be eligible5, 6, 7, 8, 9, 10, 11, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 (PRISMA chart, Fig. 1). We were able to obtain original data from only three of the included studies.8, 11, 34

A total of 3,628 patients were diagnosed with PABC and were compared with a control group of 37,100 breast cancer patients (Table 1). PABC

Discussion

To the best of our knowledge, this is the largest work to investigate the prognosis of PABC. Notably, we found that PABC is associated with poor prognosis, even after adjustment for confounding factors. We also found that PABC has a higher risk of recurrence compared to controls. We did not find any impact on the type, time and size of the study on survival outcome.

It is known that pregnancy exert a bi-directional effect on breast cancer development with a short-term increase in risk (up to 5

Conflict of interest

The authors have declared no conflicts of interest.

Acknowledgments

Part of this work was presented as a poster presentation in the 2011 San Antonio Breast Cancer Symposium. Hatem A. Azim Jr. and Luigi Santoro contributed equally to this work. Hatem A. Azim Jr. is supported by an ESMO research grant. Fedro Peccatori is supported by the IEO and Avon foundations. We would like to thank Dr. Sayed A. Aziz for providing original patient information for his study.34

References (47)

  • H. Stensheim et al.

    Cause-specific survival for women diagnosed with cancer during pregnancy or lactation: a registry-based cohort study

    J Clin Oncol

    (2009)
  • M.J. Halaska et al.

    Presentation, management and outcome of 32 patients with pregnancy-associated breast cancer: a matched controlled study

    Breast J

    (2009)
  • A.O. Rodriguez et al.

    Evidence of poorer survival in pregnancy-associated breast cancer

    Obstet Gynecol

    (2008)
  • W.B. Moreira et al.

    Prognosis for patients diagnosed with pregnancy-associated breast cancer: a paired case-control study

    Sao Paulo Med J

    (2010)
  • H.A. Azim et al.

    The biological features and prognosis of breast cancer diagnosed during pregnancy: a case-control study

    Acta Oncol

    (2012)
  • S. Greenland

    Quantitative methods in the review of epidemiologic literature

    Epidemiol Rev

    (1987)
  • B. Woolf

    On estimating the relation between blood group and disease

    Ann Hum Genet

    (1955)
  • M.K. Parmar et al.

    Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints

    Stat Med

    (1998)
  • J.P. Higgins et al.

    Quantifying heterogeneity in a meta-analysis

    Stat Med

    (2002)
  • P. Macaskill et al.

    A comparison of methods to detect publication bias in meta-analysis

    Stat Med

    (2001)
  • J.S. Mausner et al.

    Cancer of the breast in Philadelphia hospitals 1951–1964

    Cancer

    (1969)
  • A. Wallgren et al.

    Carcinoma of the breast in women under 30 years of age: a clinical and histopathological study of all cases reported as carcinoma to the Swedish Cancer Registry, 1958–1968

    Cancer

    (1977)
  • P. Nugent et al.

    Breast cancer and pregnancy

    Arch Surg

    (1985)
  • Cited by (194)

    • Breast cancer treatment and ovarian function

      2023, Reproductive BioMedicine Online
    View all citing articles on Scopus
    View full text