In Reply

Abstract

We read with concern the review by Guray and Sahin [1] that adds to the body of evidence on clinical features and practical management of benign breast diseases (BBDs) [2]. We believe that the aspects regarding fibrocystic changes contained in the article deserve some comments (in particular for cystic lesions), and furthermore, several caveats are implicit (the data tend to be correlative rather than mechanistic in nature).Although the most common presenting symptoms of fibrocystic changes (FCCs) are breast pain and tender nodularities in the breast, most breast cysts (especially microcysts) are not painful, not progressive, and spontaneously regress. It is therefore possible for women to live their lives in blissful ignorance of the fact that they have a cyst: these women would be those who do not examine their breasts and do not have a heightened awareness of breast cancer (BC). By contrast, the women who discover palpable macrocysts in the breast are those who may practice self-examination and are BC aware [3]. These two groups of women are likely to be very different in terms of other risk factors, and potential epidemiological differences (e.g., a family history of BC, postponement of the first pregnancy, use of the pill, and use of hormone-replacement therapy). These determinants lead to the pathogenesis of BC in women with a history of gross cystic breast disease (GCBD) [4].Moreover, an overview of GCBD studies carried out during the last 30 years sheds light on the different biochemical, molecular, and morphological differences of the two breast gross cyst types [5], providing evidence that the peculiar electrolyte, protein, sex hormone, growth factor, and proteolytic enzyme accumulation reflects both the biochemical environment and the morphological aspect of the epithelium lining the gross cysts, developing into the terminal duct-lobular unit. The different biocompound profiles found in the flattened low-risk and apocrine high-risk gross cysts may aid in the classification of gross cyst subtypes [6] and the identification of a biomolecular/morphological pattern [4,5,7,8] in women with a history of GCBD who go on to develop subsequent breast cancer [9][10][11]. These gross cyst types also differ in their natural history, particularly in terms of multiplicity and recurrence [11, 12]. Although care should be taken in translating the potential biological activity of several constituents (e.g., mitogenic growth factors, steroid hormones, proteolytic enzymes) into trophic effects within the breast and subsequent BC risk, gross cysts lined by apocrine epithelium show the ability to actively synthesize and secrete bioactive molecules [5], strengthening the epidemiological evidence of the increased risk for BC in GCBD-affected women [12].The best evaluation of FCCs should take into account the natural history of some BBDs [4,10], and cytomorphology may be helpful to discern between nonproliferative and proliferative lesions, with and without atypia, through an accurate cytology index [13]. In this respect, s...