Pattern of recurrence of early breast cancer is different according to intrinsic subtype and proliferation index

Abstract

IntroductionRecurrence risk in breast cancer varies throughout the follow-up time. We examined if these changes are related to the level of expression of the proliferation pathway and intrinsic subtypes.MethodsExpression of estrogen and progesterone receptor, Ki-67, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and cytokeratin 5/6 (CK 5/6) was performed on tissue-microarrays constructed from a large and uniformly managed series of early breast cancer patients (N = 1,249). Subtype definitions by four biomarkers were as follows: luminal A (ER + and/or PR+, HER2-, Ki-67 <14), luminal B (ER + and/or PR+, HER2-, Ki-67 ≥14), HER2-enriched (any ER, any PR, HER2+, any Ki-67), triple-negative (ER-, PR-, HER2-, any Ki-67). Subtype definitions by six biomarkers were as follows: luminal A (ER + and/or PR+, HER2-, Ki-67 <14, any CK 5/6, any EGFR), luminal B (ER + and/or PR+, HER2-, Ki-67 ≥14, any CK 5/6, any EGFR), HER2-enriched (ER-, PR-, HER2+, any Ki-67, any CK 5/6, any EGFR), Luminal-HER2 (ER + and/or PR+, HER2+, any Ki-67, any CK 5/6, any EGFR), Basal-like (ER-, PR-, HER2-, any Ki-67, CK5/6+ and/or EGFR+), triple-negative nonbasal (ER-, PR-, HER2-, any Ki-67, CK 5/6-, EGFR-). Each four- or six-marker defined intrinsic subtype was divided in two groups, with Ki-67 <14% or with Ki-67 ≥14%. Recurrence hazard rate function was determined for each intrinsic subtype as a whole and according to Ki-67 value.ResultsLuminal A displayed a slow risk increase, reaching its maximum after three years and then remained steady. Luminal B presented most of its relapses during the first five years. HER2-enriched tumors show a peak of recurrence nearly twenty months post-surgery, with a greater risk in Ki-67 ≥14%. However a second peak occurred at 72 months but the risk magnitude was greater in Ki-67 <14%. Triple negative tumors with low proliferation rate display a smooth risk curve, but with Ki-67 ≥14% show sharp peak at nearly 18 months.ConclusionsEach intrinsic subtype has a particular pattern of relapses over time which change depending on the level of activation of the proliferation pathway assessed by Ki-67. These findings could have clinical implications both on adjuvant treatment trial design and on the recommendations concerning the surveillance of patients.

Prognostic significance of Ki-67 index value at the primary breast tumor in recurrent breast cancer

“…The Ki-67 index value provides useful prognostic information beyond the traditionally assessed clinicopathological variables. It was reported that the Ki-67 index value was an independent prognostic factor in early breast cancer, particularly luminal type tumors (8,23). A multivariate analysis by Reyal et al (18) revealed that the Ki-67 index value remained the only significant prognostic factor in the subgroups of ER-positive and HER2-negative tumors.…”

Smoking Habit and Clinico-Biological Parameters of Breast Cancer

“…Considering the molecular types of IDCs [47], we observed that the luminal B subtype was less frequent in the group of smokers (6/39 vs 52/202), near statistical signifi cance (p=0,099), relationship increased when compared nonsmoker subgroup with active and former smokers subgroups together (7/50 vs 53/202; p=0,068). Although several groups have described that some of the substances found in cigarette act like estrogens, smoking has been postulated to have antiestrogenic effect and this would explain our fi ndings also that smoking is associated with an increased occurrence of hormone-receptor negative tumors [48], especially when the patients starting to smoke at an early age of </= 19 years [49,50].…”

Czy wydłużona pooperacyjna hormonoterapia powinna być standardowym postępowaniem u chorych na raka piersi? Głos na TAK

“…Dzięki zastosowaniu 5-letniego leczenia tamoksyfenem bezwzględne 10-letnie ryzyko nawrotu zostało obniżone o około 15%, co z kolei przełożyło się na 10-procentowe obniżenie 15-letniego ryzyka zgonu [1]. W przeciwieństwie do raków pozbawionych ekspresji receptorów steroidowych, w których większość nawrotów pojawia się w ciągu pierwszych kilku lat po leczeniu, wznowy raków luminalnych wystę-pują jednak często po wielu latach, a roczne ryzyko nawrotu utrzymuje się na prawie stałym poziomie przez wiele lat [2,3]. U chorych leczonych uzupełniająco przez 5 lat ponad połowa nawrotów pojawia się po upływie pierwszych pięciu lat od rozpoznania raka piersi [4].…”