Dataset Information

Proposed new clinicopathological surrogate definitions of luminal A and luminal B (HER2-negative) intrinsic breast cancer subtypes.

ABSTRACT:

Introduction

The St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013 recognized substantial progress in the pathological characterization of breast cancer subtypes. A useful surrogate definition was developed to distinguish luminal A-like breast cancer from luminal B-like disease based on a combination of estrogen receptor (ER), progesterone receptor (PgR) and Ki-67 status, without a requirement for molecular diagnostics. Differences depend upon the choice of the threshold value for Ki-67 and the requirement for substantial PgR positivity. We aimed to verify the suitability of the new surrogate definitions of luminal subtypes in terms of distant disease control in a large series of patients.

Methods

We studied 9,415 women with a median follow-up of 8.1 years who (1) had ER-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer and (2) had undergone surgery at the European Institute of Oncology between 1994 and 2006. We evaluated distant disease-free survival of patients with "low" (<14%), "intermediate" (14% to 19%) or "high" (?20%) Ki-67 positivity stratified by PgR expression (negative or low versus high). We calculated the cumulative incidence of distant events, considered competing events and performed multivariable analysis adjusted for pathologic tumor stage, pathologic node stage, tumor grade, peritumoral vascular invasion and menopausal status.

Results

Lack of substantial PgR positivity was associated with poorer outcomes only for patients with an intermediate Ki-67 level (P<0.001). The 4,890 patients (51.9%) with low Ki-67 level (any PgR expression level) or with intermediate Ki-67 level but substantial PgR positivity had comparably good outcomes and thus may represent a most advantageous grouping of those with luminal A-like disease.

Conclusions

The updated pathological definition of intrinsic molecular subtypes may maximize the number of patients classified as having the luminal A-like intrinsic subtype of breast cancer and for whom the use of cytotoxic drugs could mostly be avoided.

SUBMITTER: Maisonneuve P

PROVIDER: S-EPMC4095689 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Publications

Proposed new clinicopathological surrogate definitions of luminal A and luminal B (HER2-negative) intrinsic breast cancer subtypes.

Maisonneuve Patrick P Disalvatore Davide D Rotmensz Nicole N Curigliano Giuseppe G Colleoni Marco M Dellapasqua Silvia S Pruneri Giancarlo G Mastropasqua Mauro G MG Luini Alberto A Bassi Fabio F Pagani Gianmatteo G Viale Giuseppe G Goldhirsch Aron A

Breast cancer research : BCR 20140620 3

<h4>Introduction</h4>The St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013 recognized substantial progress in the pathological characterization of breast cancer subtypes. A useful surrogate definition was developed to distinguish luminal A-like breast cancer from luminal B-like disease based on a combination of estrogen receptor (ER), progesterone receptor (PgR) and Ki-67 status, without a requirement for molecular diagnostics. Differences depend upon th ...[more]

PMID: 24951027

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Project description:Background: Luminal B-like human epidermal growth factor receptor 2 negative (Luminal B [HER2-]) is the most common molecular subtype of breast cancer (BC). Since the relationship between Luminal B (HER2-) BC and liver metastasis (LM) is poorly defined, this retrospective study aimed to develop an LM risk nomogram for patients with lymph node-related (N + Luminal B [HER2-]) BC. Methods: Data were obtained for patients initially diagnosed with BC from the Tianjin Medical University Cancer Institute and Hospital. There were 30,975 Chinese female patients with stage I-III BC and follow-up confirming 1217 subsequent patients with LM, and 427 patients with N + Luminal B (HER2-). The LM risk was assessed using Cox proportional hazards regression, histogram, Venn diagram, and Kaplan-Meier survival analysis, with further analysis for patients with N + Luminal B (HER2-) BC. A nomogram was established based on the N + Luminal B (HER2-) BC data, which was validated using calibration plots. Results: The median age of 427 patients with N + Luminal B (HER2-) liver metastasis of breast cancer (BCLM) was 49 years. The largest number of patients with BCLM was diagnosed between the second to the 6th year, the longest interval from initial BC diagnosis to subsequent LM was 145 months. The patients with LM as the first site of distant metastasis which is associated with better survival were analyzed by Kaplan-Meier. The nomogram was constructed for the risk of LM that included age, menstrual status, unilateral oophorectomy, pregnancy, hepatitis B antigen, region of residence, tumor size, lymph node, clavicular lymph nodes, progesterone receptor, and lymph vessel invasion. Conclusion: We described the clinicopathological characteristics of patients with stage I-III BC, and constructed a nomogram for calculating personalized LM probabilities for patients with N + Luminal B (HER2-), which could guide future prolonged or early extensive treatment decisions.

Project description:BackgroundCDK4/6 inhibitors (CDKi), namely, palbociclib, ribociclib, and abemaciclib, combined with either an aromatase inhibitor (AI) or fulvestrant are the standard first/second line for hormone receptor-positive(HR+)/HER2-negative(neg) metastatic breast cancer (MBC). However, the choice of one specific CDKi is arbitrary and based on the physician's experience with the drug, toxicity profile, and patient's preferences, whereas biomarkers for optimal patient selection have not been established so far. Moreover, upfront chemotherapy is still recommended in case of clinical presentation with visceral crisis, despite no evidence of superior benefit for chemotherapy regimens against CDKi-based regimens. Recent correlative biomarker analyses from pivotal trials of palbociclib and ribociclib showed that HR+/HER2-neg MBC might respond differently according to the molecular intrinsic subtype, with Luminal A and B tumors being sensitive to both CDKi, Basal-like being insensitive to endocrine therapy, irrespective of CDKi, and HER2-enriched tumors showing a benefit only with ribociclib-based therapy.Clinical caseWe hereby present a paradigmatic clinical case of a woman affected by a relapsed HR+/HER2-neg MBC with bone and nodal lesions, presenting with a visceral crisis in the form of lymphangitis carcinomatosis and diagnosed with a molecularly HER2-enriched tumor, successfully treated with upfront ribociclib + fulvestrant. The patient experienced a complete symptomatic and radiologic remission of the lymphangitis with a partial response as best response, according to RECIST 1.1 criteria. The progression-free survival (PFS) was of 20 months, in line with the median PFS observed in the ribociclib + fulvestrant pivotal trial, where, however, patients with visceral crisis had been excluded.ConclusionsThis clinical case confirms in the real-world setting that non-luminal subtypes can be found in HR+/HER2-neg disease and may have potential therapeutic implications in the metastatic setting. It also questions the recommendation of upfront chemotherapy in the case of a visceral crisis in the era of CDKi-based regimens. These issues merit further evaluation in prospective and larger studies.

Dataset Information

Proposed new clinicopathological surrogate definitions of luminal A and luminal B (HER2-negative) intrinsic breast cancer subtypes.

Introduction

Methods

Results

Conclusions

Publications

Proposed new clinicopathological surrogate definitions of luminal A and luminal B (HER2-negative) intrinsic breast cancer subtypes.

Similar Datasets

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