VOLUME

32

䡠

NUMBER

3

䡠

JANUARY

20

2014

JOURNAL OF CLINICAL ONCOLOGY

C O R R E S P O N D E N C E

Prognosis of Women With Primary Breast Cancer Diagnosed During Pregnancy TO THE EDITOR: In the July 10, 2013, issue of Journal of Clinical Oncology, Amant et al1 reported the results from an international collaborative study on prognosis of women with primary breast cancer diagnosed during pregnancy. Their results contrast with those of a recent report2 on a meta-analysis of 30 studies derived from the literature and that showed a significantly higher risk of death for patients diagnosed during pregnancy or 1 year afterward, with a particular risk for those diagnosed postpartum; this group of patients was not included in the Amant study. In addition, there was no statistically significant difference in disease-free and overall survival at a median follow-up of 61 months in the overall group of 311 evaluable patients. The majority of these patients had triple-negative or human epidermal growth factor receptor 2–positive disease (118 and 145 patients respectively, whereas there were 145 endocrine-responsive patients overall). For these patients at higher risk, no or little effect of hormonal milieu may be anticipated, and activity of targeted agents may have contributed to improve prognosis. On the other hand, in the luminal B cohort a hazard ratio (HR) of 1.73 in overall survival with an extremely large 95% CI (0.63 to 4.75) was reported in the 109 pregnant patients. In their discussion, the authors did not mention this fact. They simply concluded that they found similar survival for patients with pri-

mary breast cancer diagnosed during pregnancy when compared with nonpregnant patients after adjusting for known prognostic factors. To better understand differences in the biology of breast cancer this may be at least in part true for triple-negative disease (HR, 1.04; 95% CI, 0.51 to 2.09) or human epidermal growth factor receptor 2–positive disease (HR, 1.34; 95% CI, 0.51 to 3.54) but may be not the case for endocrine-responsive breast cancer, given that only 46 patients were considered with luminal A and 99 patients with luminal B breast cancer (HR, 0.60; 95% CI, 0.08 to 4.68). Therefore, according to our opinion, the conclusions of the authors should be taken with caution particularly for endocrineresponsive patients. As we have no data from evidence-based studies, the issue of the recommendation to proceed with a pregnancy in young hormoneresponsive patients remains an open question.

Diana Crivellari and Loredana Militello Centro di Riferimento Oncologico, Aviano, Italy

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest. REFERENCES 1. Amant F, von Minckwitz G, Han SN, et al: Prognosis of women with primary breast cancer diagnosed during pregnancy: Results from an international collaborative study. J Clin Oncol 31:2532-2539, 2013 2. Azim HA Jr, Santoro L, Russell-Edu W, et al: Prognosis of pregnancy-associated breast cancer: A meta-analysis of 30 studies. Cancer Treat Rev 38:834-842, 2012

DOI: 10.1200/JCO.2013.52.3977; published online ahead of print at www.jco.org on December 2, 2013

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Reply to D. Crivellari et al We thank Crivellari and Militello1 for their comments on our recent article2 regarding the noninferior prognosis of 311 women with breast cancer diagnosed during pregnancy as compared with a cohort of 865 nonpregnant women. Two main concerns were raised: first, that we did not include the meta-analysis by Azim et al,3 in which pregnancy-associated breast cancer was found to have worse prognosis; second, the concern that pregnancy especially fuels hormone receptor–positive breast cancer. Historically, pregnancy-associated breast cancer was considered one entity and defined as breast cancer diagnosed during pregnancy (BCP) or within 1 to 2 years after delivery. Recent studies have shown that a diagnosis in the postpartum period has worse prognosis.4 A possible explanation is that physiologic mechanisms of postpartum mammary gland involution mimic a wound healing environment and can be protumorigenic, which likely accounts for the poor prognosis of postpartum breast cancer (PPBC).5 For this reason, we specifically excluded all studies from our literature review that did not differentiate between BCP and PPBC. The meta-analysis by Azim et al3 was not based on individual patient data and no subdifferentiation was made between the pregnant and the postJournal of Clinical Oncology, Vol 32, No 3 (January 20), 2014: pp 255-263

partum groups in the primary analysis, thereby precluding differences between BCP and PPBC. When focusing on adjusted hazard ratios (HR) from multivariable models, patients diagnosed with PPBC had a clear trend of poorer overall survival (pooled HR, 1.84; 95% CI, 1.28 to 2.65), which was less apparent in patients with BCP (pooled HR, 1.29; 95% CI, 0.74to2.24).Thislatterresultissimilartothatinourstudy(HR,1.19;95% CI, 0.73 to 1.93).2 The second concern is whether pregnancy negatively influences hormone receptor–positive breast cancer. We agree with Crivellari et al1 that our group of patients is too small to draw firm conclusions from the subgroup analyses of luminal A and luminal B disease. However, the proportion of hormone receptor–positive and hormone receptor–negative disease is fairly evenly distributed (46.6% and 53.4%, respectively, for estrogen receptor/progesterone receptor– positive and estrogen receptor/progesterone receptor–negative disease). In the subgroup of patients with hormone receptor–positive disease the HR for disease-free and overall survival was 1.20 (95% CI, 0.66 to 2.19; P ⫽ .68) and 1.39 (95% CI, 0.59 to 3.34; P ⫽ .68), respectively. For luminal A disease, the HR was 0.60, although the 95% CI was wide (0.08 to 4.68). Use of multivariable Cox proportional hazards regression model to adjust for exposure (pregnant or not), age, stage, grade, hormone receptor status, human epidermal growth © 2013 by American Society of Clinical Oncology

Information downloaded from jco.ascopubs.org and provided by at NEW YORK UNIVERSITY MED CTR on October 4, 2014 Copyright © 2014 Americanfrom Society of Clinical Oncology. All rights reserved. 128.122.253.212

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