Mammary gland architecture as a determining factor in the susceptibility of the human breast to cancer.

The developmental pattern of the breast can be assessed by determining the composition of the breast in specific lobular structures, which are designated as lobules type 1 (Lob 1), lobules type 2 (Lob 2), and lobules type 3 (Lob 3), with Lob 1 being the less developed and Lob 3 being the most differentiated or with the highest number of ductules per lobular unit. In the present work, the patient population consisted of three groups of women who underwent surgical procedures: The first group included women who underwent reduction mammoplasty (RM) for cosmetic reasons. The second group included women who underwent prophylactic subcutaneous mastectomy after genetic counseling for either carrying the BRCA-1 gene or belonging to a pedigree with familial breast cancer (FAM), and the third group included women who underwent modified radical mastectomy (MRM) for the diagnosis of invasive carcinoma. The RM group consisted of 33 women, of whom 9 were nulliparous and 24 were parous. The FAM group consisted of 17 women, of whom 8 were nulliparous and 9 were parous. The MRM group consisted of 43 women, of whom 7 were nulliparous and 36 were parous. The analysis of the lobular composition of all of the samples from the RM group, which is considered the control group, revealed that Lob 1 represented 22%, Lob 2 represented 37%, and Lob 3 represented 38%, whereas the tissue examined from the FAM and MRM groups contained a preponderance of Lob 1 at 48% and 74%, respectively, over Lob 3, which was 10% and 3%, respectively. When the results of the analysis of breast tissue were separated according to the pregnancy history of the donor, it was found that in the control group or RM, there was a significant difference in lobular composition. Nulliparous women of the RM group showed a preponderance of Lob 1 (46%) over parous women, which contained only 17%, whereas the percentage of Lob 3 in the nulliparous group was significantly lower (7%) than the parous group (48%). In the breast tissues obtained from FAM and MRM, no significant differences in lobular composition were observed, as all of the samples contained a higher concentration of Lob 1, independent of the pregnancy history. The breast tissue of FAM and MRM of parous women had a developmental pattern that was similar to that of nulliparous women of the same group and that was less developed than the breast of parous women of the control group. An important difference between the Lob 1 of the FAM group versus the control (RM) and the MRM group was that most of these lobules had thin ductules with an increase in hyalinization of the intralobular stroma manifested in the whole-mount preparation as an alteration in the branching pattern. The data suggest that the breast tissue of women with invasive cancer, as well as those from a background of familial breast cancer, have an architectural pattern different from the control or normal tissues and that the BRCA-1 or related genes may have a functional role in the branching pattern of the breast during lobular development, mainly in the epithelial stroma interaction.