Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy

Abstract

Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy.Alkner, Sara; Ehinger, Anna; Bendahl, Pär-Ola; Rydén, Lisa; Fernö, Mårten Link to publication Citation for published version (APA): Alkner, S., Ehinger, A., Bendahl, P-O., Rydén, L., & Fernö, M. (2015). Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy. European Journal of Cancer, 51(16), 2304 -2313 . DOI: 10.1016 /j.ejca.2015 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Role of the Funding Sources:None of the funding sources had any impact on study design; the collection, analysis and interpretation of data; the writing of the report; or in the decision to submit the article for publication.3 Abstract Aim: A contralateral breast cancer (CBC) is today treated as an independent primary tumor, although recent data suggest risk and prognosis of CBC to be influenced by characteristics of and treatment given for the first tumor (BC1). We hereby investigate phenotypical and prognostic features of the second tumor (BC2) in relation to prior endocrine treatment and radiotherapy.Methods: From a well-defined population-based cohort of CBC-patients, we have constructed a unique tissue-microarray including 600 pairs of primary tumors and CBCs.Breast cancer mortality was primary end-point for prognosis. Results: Both estrogen receptor (ER) status and stage was strongly correlated between BC1and BC2 within CBC-pairs. Although BC2 had the highest prognostic impact, BC1 continued to influence prognosis after diagnosis of CBC. Patients diagnosed with two high stage tumors within a short time-interval had a particularly bad prognosis. Prior endocrine therapy and radiotherapy both correlated to ER-negativity of BC2. An ER-negative BC2 was associated with an inferior prognosis compared to an ER-positive BC2 regardless of ER-status of BC1 or prior endocrine therapy. Conclusions:Our results suggest that both the residual prognostic impact of BC1, the possibility of contralateral metastasis, as well as prior treatment given, need to be considered when determining appropriate diagnostic work-up and treatment of CBC. In addition, radiation to the contralateral breast and risk of inducing CBC with an aggressive ER-negative phenotype should be considered when establishing new radiation treatm...

Plasma membrane expression of G protein-coupled estrogen receptor (GPER)/G protein-coupled receptor 30 (GPR30) is associated with worse outcome in metachronous contralateral breast cancer

“…Previous studies by our group showed that characteristics of BC2 have the highest influence on prognosis after development of CBC, although the characteristics of BC1 continue to have some prognostic impact [33]. GPR30 PM + staining in both BC2 and LGL2 was associated with increased risk of BCD (Table 2; Fig 5A and 5B; HR BC2 = 1.7; 95% CI = 1.1-2.7; p = 0.03, and HR LGL2 = 2.0; 95% CI = 1.1-3.4; p = 0.02).…”

“…Patient inclusion and number of CBC successfully stained and scored for GPR30 are summarized in Fig 1. Followup information was retrieved from patient charts, and cause of death and overall survival data were accessed from the Swedish National Board of Health and Welfare in March 2014. Evaluation of ER, PR, Ki67 and HER2 have been previously described [26,27].…”

Stability of oestrogen and progesterone receptor antigenicity in formalin‐fixed paraffin‐embedded breast cancer tissue over time

“…For example, the CYT method changed during the time periods studied, making results in relation to PR harder to interpret. The cohort represents patients with CBC, and although our previous studies have shown BC2 to be the major determinant of prognosis after the development of CBC , the prognosis after BC2 could still be affected by the first breast cancer. However, as the same cohort was analysed in relation to prognosis for both CYT/IHC, this should not affect our results.…”

“…For this study, a TMA of patients with contralateral breast cancer (CBC) was used. Inclusion criteria, data abstraction and TMA construction, as well as prognosis and ER/PR status in relation to both tumours and treatment, have been described previously . The TMA included a total of 1328 tumours from 728 patients.…”

“…As ER‐negative BCs are more often HER2‐positive and Ki67‐high , the proportion of HER2‐positive (IHC 3+) and Ki67‐high (>20%) tumours in relation to ER IHC over time was investigated as a surrogate marker of ER IHC stability. We have previously shown the ER status of the second breast cancer (BC2) to be important for prognosis after CBC diagnosis , with a worse BCM for patients with ER‐negative tumours. Hence, survival after BC2 was analysed in relation to ER status with IHC/CYT in order to investigate which method gave the best prognostic information and, hence, probably the most reliable ER evaluation.…”