Prognostic molecular markers in women aged 35 years or younger with breast cancer: is there a difference from the older patients?

Lin, Ching-Hung; Lu, Yen‐Shen; Huang, Chiun‐Sheng; Kuo, Kuan‐Ting; Wang, Chung Chieh; You, San–Lin; Lin, P.C.; Chang, Daw-Yuan; Kuo, Wen‐Hung; Chang, King‐Jen; Cheng, Ann‐Lii

doi:10.1136/jclinpath-2011-200064

Cited by 8 publications

(3 citation statements)

References 29 publications

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“…After screenings, 68 articles were chosen for further full-text review. Ultimately, 32 eligible studies were included in our meta-analysis59101112131415161718192021222324252627282930313233343536373839 (Figure 1). …”

Section: Resultsmentioning

confidence: 99%

Prognostic role of PIK3CA mutations and their association with hormone receptor expression in breast cancer: a meta-analysis

Pang

Cheng

Sun

et al. 2014

Sci Rep

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The phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene is frequently mutated in breast cancer (BCa). Sex hormone receptors (HRs), including estrogen receptor (ER) and progesterone receptor (PR) play pivotal roles in BCa. In this study, we evaluated the association between PIK3CA mutations and ER/PR expression and the prognostic role of PIK3CA mutations in BCa patients, and in particular, HR-positive BCa. Thirty-two studies involving 5719 cases of BCa obtained from database searches were examined. PIK3CA gene mutations correlated significantly with ER/PR expression (p < 0.00001) and relapse-free survival (RFS) (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59–0.98, p = 0.03) but not overall survival (OS) (HR 1.14, 95%CI 0.72–1.82, p = 0.57) in unsorted BCa patients. PIK3CA mutations were not associated with OS (HR 1.06, 95%CI 0.67–1.67, p = 0.81) or RFS (HR 0.86, 95%CI 0.53–1.40, p = 0.55) in HR-positive BCa patients. In conclusion, PIK3CA mutations were significantly related to ER/PR expression and RFS in unsorted BCa patients. However, the clinical implications of PIK3CA mutations may vary according to different mutant exons. And PIK3CA mutations alone may have limited prognostic value for HR-positive BCa patients.

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Section: Resultsmentioning

confidence: 99%

Prognostic role of PIK3CA mutations and their association with hormone receptor expression in breast cancer: a meta-analysis

Pang

Cheng

Sun

et al. 2014

Sci Rep

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“…These results could partly be explained by the fact that young women are diagnosed more often at advanced stages, present unfavorable tumour characteristics or have a family history of breast cancer [6][7][8][9]. In a very recent study of Lin et al it is suggested that these cancers occurring at a very young age may be considered as a distinct disease entity [10]. Due to the relatively low frequency of breast carcinomas in women aged ≤35 years there are few data on how risk factors predict breast cancer in younger women and the prognostic factors in this group have yet to be established.…”

Section: Introductionmentioning

confidence: 89%

“…In the study of Lin et al it is presented that for women ≤35 years high Ki67 expression, TP53 mutations, ER negative status and HER2 overexpression were associated with shorter overall survival, and TP53 mutations, Ki67, HER2 overexpression are strong prognostic factors for these women [10].…”

Section: Introductionmentioning

confidence: 99%

Retrospective Analysis of Clinicopathological Characteristics and Family History Data of Early-Onset Breast Cancer: A Single-Institutional Study of Hungarian Patients

Madaras

Baranyák²,

Kulka

et al. 2013

Pathol. Oncol. Res.

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Patients at young age (≤35 years) diagnosed with breast cancer (BC) are considered to have poor prognosis. The aim of the present study was to retrospectively analyse clinicopathological characteristics and prognosis in a group of young BC patients. We included women diagnosed with invasive breast carcinoma younger than/or at the age of 35 years. Between 1999 and 2009, 107 women with earlyonset BC were selected from the database of the 2nd Department of Pathology at Semmelweis University. For clinicopathological comparison, 55 women (36-45 years), 214 women (46-65 years), 110 women (66-75 years) and 58 women (76≤years) were also included in the analysis. Family history, clinicopathological and follow-up data were analysed. The tissue specimens were reviewed for histological type, nuclear grade, and estrogen receptor (ER), progesterone receptor (PgR), Ki67 and HER2 status (IHC4). The mean age in the study group was 31.6 years at the time of diagnosis. Histology showed a high incidence of grade III tumours in this group of patients (67.9 %), while only four cases (3.8 %) were considered grade I. According to the immunohistochemical results, 35.3 % of the study cases were considered as Luminal B (LumB: either being higly proliferative or co-expressing HER2) and 33.3 % as triple negative breast carcinomas (TNBC). The detailed questionnaire related to family history was completed and received in 49/107 cases (45.8 %). Analysis of these data revealed an affected family history of breast or ovarian carcinoma in first and second degree relatives in 51.0 %. A high proportion (52.0 %) of TNBC was observed among young women with a family history of the disease. Survival analysis of the 107 patients showed that 25 (23.3 %) women died until 31 December 2012. No significant difference in survival was detectable considering the regimen of systemic treatment (p=0.188). Regarding clinicopathological parameters, the immunophenotypes, grade, pT and pN values differred substantially between the age groups (p=0.001, for all), and the shortest relapse-free survival was seen among the youngest BC patients. This analysis illustrates that breast cancer arising in young women is characterized by the presence of less favorable subtypes such as LumB and TNBC. The increased proportion of TNBC was especially remarquable in the Lilla Madaras and Zsuzsanna Baranyák equal contribution. Oncol. Res. (2013) 19:723-729 DOI 10.1007 group of patients presenting with family history of the disease. The fact that a high rate of death occured and no significant difference in OS were notable regarding the scheme of systemic therapies (neoadjuvant vs. adjuvant) highlight the necessity of the development of new treatment strategies. Electronic supplementary material

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Prognostic value of different cut-off levels of Ki-67 in breast cancer: a systematic review and meta-analysis of 64,196 patients

Petrelli

Viale

Cabiddu

et al. 2015

Breast Cancer Res Treat

221

151

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A proliferative marker, expressed as the percentage of cells in a cell cycle, has been developed and used as a discriminant of more aggressive malignant phenotypes in early breast cancer (BC). The marker is usually expressed by the immunohistochemical staining of the cell cycle antigen Ki-67. It has not, however, yet been definitely evaluated, due to methodological concerns, which specific Ki-67 cut-off provide the strongest prognostic information in resected BC. We conducted a meta-analysis to explore the prognostic value of different cut-off levels of Ki-67 in terms of overall survival (OS) and disease-free survival (DFS) in early BC. The databases of PubMed, the ISI Web of Science, EMBASE, SCOPUS, the Cochrane Central Register of Controlled Trials, and CINHAL were used to identify the relevant literature. Data from studies reporting a hazard ratio (HR) and a 95 % confidence interval (CI) calculated as a multivariate analysis were pooled in a meta-analysis, with metaregression used to test for trends in predefined subgroups. All the statistical tests were 2-sided. Forty-one studies encompassing 64,196 BC patients were included in the analysis. Overall, n = 25 studies were available for the OS analysis. The pooled HR for high versus low Ki-67 was 1.57 (95 % CI 1.33-1.87, P < 0.00001). Twenty-nine studies were available for the DFS analysis. The pooled HR for high versus low Ki-67 was 1.50 (95 % CI 1.34-1.69, P < 0.00001). When a cut-off of Ki-67 staining ≥ 25 % was used, the pooled HR for OS was 2.05 (95 % CI 1.66-2.53, P < 0.00001), which was significantly different to studies where the cut-offs chosen were <25 %. In ER+ tumors, the HR for high versus low Ki-67 was similar and significant (HR = 1.51, 95 % CI 1.25-1.81, P < 0.0001). We conclude that Ki-67 has an independent prognostic value in terms of OS in BC patients. The Ki-67 threshold with the greatest prognostic significance is as yet unknown, but a cut-off >25 % is associated with a greater risk of death compared with lower expression rates.

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Prognostic molecular markers in women aged 35 years or younger with breast cancer: is there a difference from the older patients?

Abstract: For women ≤ 35 years, TP53 mutations, Ki67 and HER2 expressions are strong prognostic factors. The limited prognostic value of hormone receptors suggests that the prognostic markers used in age-unspecified breast cancer may not be completely fit for this population.

Cited by 8 publications

References 29 publications

Prognostic role of PIK3CA mutations and their association with hormone receptor expression in breast cancer: a meta-analysis

Prognostic role of PIK3CA mutations and their association with hormone receptor expression in breast cancer: a meta-analysis

Retrospective Analysis of Clinicopathological Characteristics and Family History Data of Early-Onset Breast Cancer: A Single-Institutional Study of Hungarian Patients

Prognostic value of different cut-off levels of Ki-67 in breast cancer: a systematic review and meta-analysis of 64,196 patients

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