The impact of progesterone receptor expression on prognosis of patients with rapidly proliferating, hormone receptor-positive early breast cancer: apost hocanalysis of the IBIS 3 trial

Abstract

Background: In the Italian Breast Cancer Intergroup Studies (IBIS) 3 phase III trial, we compared cyclophosphamide, methotrexate, 5-fluorouracil (CMF) alone to sequential epirubicin/CMF regimens in patients with rapidly proliferating early breast cancer (RPEBC). We performed a post hoc analysis in the subgroup of patients with hormone-receptor-positive RPEBC on the prognostic role of progesterone receptor (PgR) status. Methods: RPEBC was defined by thymidine labeling index (TLI) >3% or grade 3 or S-phase >10% or Ki67 >20%. We analyzed 466 patients with hormone-receptor-positive RPEBC receiving sequential epirubicin/CMF regimens followed by tamoxifen, and for whom the status of ER and PgR was available. Results: Considering both cut-off values of 10% and 20%, PgR expression was significantly associated with age, menopausal status, and ER expression; HER2 status was associated with PgR status only at a cutoff value of 20% PgR. Upon univariate analysis, tumor size, nodal status, and PgR were significantly associated with disease-free survival (DFS) and overall survival (OS), while age class and local treatment type were associated only with DFS. Patients with PgR <20% showed lower 5- and 10-year DFS [hazard ratio (HR) = 1.48; 95%CI: 1.01–2.18; p = 0.044] and OS (HR = 1.85; 95%CI: 1.08–3.19, p = 0.025) rates compared with patients with PgR ⩾20%. Upon multivariate analysis, only tumor size, nodal status, and PgR were independent prognostic factors. Conclusions: Our results highlight the independent prognostic relevance of PgR expression in patients with hormone-receptor-positive RPEBC treated with adjuvant chemotherapy and endocrine therapy, where the definition of prognostic subgroups is still a major need.

Can Estrogen Receptor, Progesterone Receptor, and Proliferative Index be Considered as Isolated Prognostic Factors of Overall Survival in Early luminal Breast Cancer?

“…In study of Bracvaccini et al only PR status in early luminal breast cancer was associated with OS and DFS among biological features. Namely, when the cutoff of PR was either <10% or <20% the patients had 5-and 10-years OS rates of 92% and 80%, respectively, compared with 95% and 89% for PR >10% [27]. Another study showed that PR expression in ER-positive early Luminal A was a significant independent prognostic factor and the difference of prognosis between PR-positive and PR-negative tumors became evident more than 5 years after surgery, resulting in better prognosis in PR-negative than in Luminal B type [16].…”

“…PR expression and Ki-67 using IHC are important prognostic factors in ER-positive early luminal breast cancers, which suggests PR's utility as a marker for differentiation between Luminal A and Luminal B subtypes [24]. The studies showed that lack of PR expression is significantly associated with poorer prognosis in luminal breast cancers [27], independently of other factors [28], and PR-positive breast cancer had a better prognosis with regard to OS and DFS [24].…”

The impact of progesterone receptor negativity on oncological outcomes in oestrogen-receptor-positive breast cancer

“…At present PgR status is not considered to confer selective advantage between EHT types 45 and ER status remains the only factor predictive of tamoxifen benefit 46 . However, the absence of this synergistic response to EHT and relative endocrine resistance is a possible explanation for the worse outcomes associated with PgR- disease 14–16 , 21 , 43 , 44 , 47 . Given these data, perhaps conscious consideration should be given to novel therapeutic strategies when treating patients with the PgR- subtype, particularly in cases of HER2- disease where the option of targeted anti-HER2 therapy or systemic chemotherapy may not be clinically indicated 19 , 20 .…”

Generation and Characterization of Novel Diagnostic Mouse Monoclonal Antibodies Against Human Estrogen Receptor Alpha and Progesterone Receptor

“…The expression of ER is a good prognostic marker of clinical outcome in breast cancer and a useful predictive marker of response to adjuvant therapy (Louie and Sevigny, 2017). PR expression is also an independent valuable prognostic biomarker in breast cancer, and its expression level must be taken into account when deciding on adjuvant treatments in patients with hormone-receptor-positive early breast cancer (Bravaccini et al, 2020).…”