JNCI J Natl Cancer Inst (2015) 107(4): djv031 doi: 10.1093/jnci/djv031 First published online February 25, 2015 Correspondence

correspondence RE: How Many Etiological Subtypes of Breast Cancer: Two, Three, Four, or More?

Affiliation of authors: Clinical and Descriptive Epidemiology Unit, Institute for Study and Cancer Prevention, Florence, Italy (AC, EC). Correspondence to: A. Caldarella, MD, Clinical and Descriptive Epidemiology Unit, Institute for Study and Cancer Prevention, via delle Oblate 2-50141 Florence, Italy (e-mail: [email protected]).

We read with great interest the article by Anderson et al. (1). The authors showed a bimodal peak distribution of age frequencies in patients with breast cancer and suggested the presence of two etiologic classes of breast cancer. Concerning the status of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) as biomarkers, in a population-based series of invasive breast cancer, we analyzed 1478 cases diagnosed in 2004 and 2005 and retrieved from the Tuscan Cancer Registry (2). We evaluated through Kernel density estimation the density plot for ER-positive tumors, and we found a bimodal age distribution at diagnosis, as described by Anderson et al. (1), with a dominant late-onset mode near age 70 years and a minor mode around age 50  years. Conversely, our results on ER-negative tumors showed a unimodal age distribution at diagnosis, with

only a late-onset mode around age 70 years (Figure 1). Moreover, when we also analyzed HER2 status by immunohistochemistry and we distinguished, according to the literature (3), four subgroups, we found that a clear bimodal distribution was present only for luminal A  breast cancer (ER+, HER2-). The other subgroups of breast cancer showed different behaviors: luminal B cancer (ER+, HER2+) incidence rates rose continuously and slowly until age 50 years, then flattened and, after age 70 years, fell; triple-negative cancer (ER-, HER2-) incidence rates increased rapidly early in life and then flattened, while HER2+ cancer (ER-, HER2+) incidence rates remained in between the luminal and triple-negative cancer rates (data not shown). The absence of the dominant early-onset mode near age 50 years in ER-negative tumors in our results, differently from the data shown by Anderson et al. (1), could be because of the small

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A. Caldarella, E. Crocetti

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Figure 1.  Tuscan Cancer Registry: age distribution in estrogen receptor–negative breast tumors.

Received: December 9, 2014; Accepted: January 26, 2015 © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: [email protected].

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References 1. Anderson WF, Rosenberg PS, Prat A, Perou CM, Sherman ME. How many etiological subtypes of breast cancer: two, three, four, or more? J Natl Cancer Inst. 2014;106(8):XXXXXX. 2. Caldarella A, Crocetti E, Bianchi S, et al. Female breast cancer status according to ER, PR and HER2 expression: a population based analysis. Pathol Oncol Res. 2011;17(3):753–758. 3. Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thurlimann B, Senn HJ & Panel Members. Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol. 2009;20(8):1319–1329. 4. Anderson WF, Reiner AS, Matsuno RK, Pfeiffer RM. Shifting breast cancer trends in the United States. J Clin Oncol. 2007;25(25):3923–3929.

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size of our population study. However, the influence of a different geographical distribution or of time-related changes in age distribution in patients with breast cancers cannot be excluded. Our cases were diagnosed in a more recent period than the cases reported by Anderson et al. (2004–2005 vs 1995–1998), and in our country a screening program has been active from the early 1990s. Time-related changes in age distribution at diagnosis, shifting from younger to older ages at diagnosis, and a shift toward low-grade breast cancers over time, although more in older than in younger women, have been previously described (4). To explain these features, an influence of the interaction between age-related biological factors and screening phenomena has been also suggested (4). Thus, we think that to explore the age distribution of breast cancer by subtypes and to identify factors responsible for the differences observed, further studies on large populations, particularly for recent years and different countries, are needed.

correspondence

RE: How many etiological subtypes of breast cancer: two, three, four, or more?

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