Recurrence and mortality dynamics for breast cancer patients undergoing mastectomy according to estrogen receptor status: Different mortality but similar recurrence

Abstract

The purpose was to ascertain whether the recurrence risk patterns for patients with estrogen receptor (ER)-positive (P) and ER-negative (N) breast cancer support the ER-related clinical divergence suggested by the observed different mortality patterns and gene expression profiles. Both recurrence and death were considered in a series of 771 patients undergoing mastectomy. ER status was available for 539 patients. The hazard rates for recurrence and mortality throughout 15 years of follow-up were assessed. The recurrence dynamics displays a bimodal pattern for both ERP and ERN tumors with comparable peak timings. The two curves cross during the 3rd year. By contrast, the mortality dynamics are definitely different for ERP and ERN tumors: during the early followup period ERN patients have their highest mortality risk, while ERP patients have their lowest mortality risk. The two curves cross during the 5th year. In spite of the different mortality dynamics, the recurrence dynamics do not demonstrate a major distinction in timing between ERP and ERN breast cancers, suggesting that the metastasis development process following mastectomy is apparently similar for both ER categories. The observed differences in the mortality risk are plausibly attributable to ER-related factors influencing the clinical course from recurrence to death. These clinical findings apparently contradict the occurrence of two different types of breast cancer, notwithstanding the distinct epidemiological, clinical, and molecular features linked to ERP and ERN tumors, although ER levels may concur to establish the event risk levels. (Cancer Sci 2010; 101: 826-830) S ince their detection, the steroid receptors were considered a reliable prognostic factor for recurrence and survival of early breast cancer.(1,2) This notion was challenged when both the more mature follow-up and the increased sample size of studies showed that the relationships weakened (3) and further investigations confirmed that the prognostic effect of the estrogen receptor (ER) content varies over time.(4-7) In particular, Hilsenbeck et al. (8) analyzed the disease-free survival in a large sample of breast cancer cases with up to 17 years of follow-up, and confirmed a remarkable crossover effect of the ER expression after about 3 years.At the population level, it was reported that the classically recognized inflection point in age-specific breast cancer rates at menopause [Clemmesen's Hook (9) ] reflects the convergence of two different rate curves, according to ER expression.(10) Both ER-positive (ERP) and ER-negative (ERN) tumors show a bimodal breast cancer population with peak frequencies near age 50 and 70 years. The first peak is dominant for ERN tumors, while ERP tumors display a higher second peak. A similar incidence pattern was even observed for other prognostic factors (size, grade, progesterone receptor (PR) expression, axillary node invasion) when categorized in a dichotomous way. Moreover, the hazard function for breast cancer death revealed quite different p...

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