Fluctuation of HER2 expression in breast: Carcinomas during the menstrual cycle

Andrea Balsari, Patrizia Casalini, Elda Tagliabue, Marco Greco, Silvana Pilotti, Roberto Agresti, Riccardo Giovanazzi, Loredana Alasio, Cristiano Rumio, Natale Cascinelli, Maria Ines Colnaghi, Sylvie Ménard

Research output: Contribution to journalArticle


The hormonal milieu at time of tumor surgery seems to have a significant impact on survival in premenopausal breast cancer patients. Indeed, surgery performed during the follicular phase of the menstrual cycle was suggested to correlate with a poor prognosis. To investigate the relationship between prognosis and menstrual cycle at time of surgery, we analyzed the expression of some markers associated with tumor aggressiveness, such as the hormone receptors, HER2, p53, Bc12, 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 hormone receptor-positive tumors. In actual fact, 20% of the tumors removed during the follicular phase scored HER2-positive, versus 8% of those removed during the luteal phase. Similarly, a number of hormone receptor-positive tumor specimens, obtained from the same patients during follicular and luteal phases, were scored HER2-positive when the sample was removed during the follicular phase and HER2-negative when removed in the luteal phase. Southern blot analysis of the HER2 gene indicated that, in hormone receptor-positive cases, the overexpression of HER2 is often not associated with gene amplification. The finding that overexpression of the HER2 gene, associated with tumor aggressiveness, can fluctuate according to the hormonal milieu may explain the increased survival of patients operated during the luteal phase. It is also relevant to the selection and treatment of patients most likely to benefit from anti-HER2 antibody therapy.

Original languageEnglish
Pages (from-to)1543-1547
Number of pages5
JournalAmerican Journal of Pathology
Issue number5
Publication statusPublished - Nov 1999

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Balsari, A., Casalini, P., Tagliabue, E., Greco, M., Pilotti, S., Agresti, R., Giovanazzi, R., Alasio, L., Rumio, C., Cascinelli, N., Colnaghi, M. I., & Ménard, S. (1999). Fluctuation of HER2 expression in breast: Carcinomas during the menstrual cycle. American Journal of Pathology, 155(5), 1543-1547.