Fluctuation of HER2 expression in breast carcinomas during the menstrual cycle

The hormonal milieu at time of tumor surgery seems to have a significant im pact on survival in premenopausal breast cancer patients. Indeed, surgery p erformed during the follicular phase of the menstrual cycle was suggested t o correlate with a poor prognosis, To investigate the relationship between prognosis and menstrual cycle at time of surgery, we analyzed the expressio n of some markers associated with tumor aggressiveness, such as the hormone receptors, HER2, p53, Bcl2, and cathepsin D in breast carcinomas obtained from 198 premenopausal women who underwent surgery during different phases of the menstrual cycle. HER2 overexpression was found to fluctuate in hormo ne receptor-positive tumors. In actual fact, 20% of the tumors removed duri ng the follicular phase scored HER2-positive, versus 8% of those removed du ring the luteal phase. Similarly, a number of hormone receptor-positive tum or specimens, obtained from the same patients during follicular and luteal phases, were scored HER2-positive when the sample was removed during the fo llicular phase and HER2-negative when removed in the luteal phase, Southern blot analysis of the HER2 gene indicated that, in hormone receptor-positiv e cases, the overexpression of HER2 is often not associated or with gene am plification. The finding that overexpression of the HER2 gene, associated w ith tumor aggressiveness, can fluctuate according to the hormonal milieu ma y explain the increased survival of patients operated during the luteal pha se. It is also relevant to the selection and treatment of patients most lik ely to benefit from anti-HER2 antibody therapy.