Morphological changes in breast tissue with menstrual cycle

Whether the breast tissue undergoes morphologic changes in relation to the menstrual cycle had been a subject of debate. Elegant studies performed in the early 1980s provided conclusive evidence of cyclical changes in the normal breast lobules. These studies were almost entirely based on autopsy material and have not been validated in the clinical setting. In the present study, we examine breast tissues from surgical specimens from 73 premenopausal women and use morphological criteria to characterize the stage of the menstrual cycle. Patients taking oral contraceptives or hormonal therapy were excluded from this study. The following histological parameters were used to assess the menstrual stage: number of cell layers in the acini and presence and degree of vacuolation of the myoepithelial cells, stromal edema, infiltrate, mitosis, and apoptosis. The morphological stage was then correlated with the stage of the cycle, as determined by last menstrual period and the usual menstrual cycle length and in some patients with serum estrogen and progesterone levels. The morphologic stage was concordant with dates in 54 of the 73 patients (74%, P = .001). In 31 of these patients, serum levels of estradiol and progesterone at the time of surgery were available for correlation. Twenty-five (80%) of these were phase concordant by morphology and progesterone levels (P = .01), and 25 (80%), by dates and progesterone levels (P = .007). Women with a high morphologic score were seven times as likely to be in luteal phase as were women with a low score (odds ratio, 7.1; 95% confidence interval). Menstrual phase can be determined by the morphology of the normal lobules present within the surgically excised breast specimens. This will permit retrospective analysis of large archival databases to analyze the effect of timing of surgery in relation to menstrual cycle phase. It will also aid the design of epidemiological studies for breast cancer risk assessment.