Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy
Introduction
Prior breast cancer patients have a life-time risk of 2–20% of developing a contralateral breast cancer (CBC) [1], [2], [3]. A CBC is today treated as a new independent primary tumour, although recent data suggest that the second tumour (BC2) may in some cases be a metastasis of the first (BC1) [4], [5]. In addition, CBC diagnosed in close connection to prior adjuvant treatment is presumably resistant to the treatment given. Indeed, prior endocrine therapy, chemotherapy and radiotherapy have all been associated with a worse prognosis once diagnosed with CBC [4], [6], [7]. CBC may hence be used as an in vivo model for studies of adjuvant treatment resistance. In addition, with new radiotherapy techniques becoming clinically available, importance of scattered dose to the contralateral breast and risk of radiation induced CBC need to be further evaluated.
We have hereby studied TNM-stage, oestrogen (ER) and progesterone receptor (PR) status of BC2 in relation to characteristics of BC1 and prior treatment, using a unique tissue-microarray (TMA) including >700 CBC-patients. This is to our knowledge the largest cohort of CBC-patients with access to detailed patient, tumour and treatment information as well as tumour tissue ever studied. We hereby wish to clarify the biological relationship between CBC-pairs, and find indications as to when contralateral metastasis should be suspected and clonal relationship further investigated. We also want to investigate phenotypical and prognostic features of BC2 in relation to prior treatment. This could not only give us important information on how to optimise treatment for patients with CBC, but also increase our knowledge on treatment escape mechanisms in vivo.
Section snippets
Tissue microarray and immunohistochemistry
Inclusion criteria and data abstraction have been described before [4]. Briefly all patients within the Southern Swedish Healthcare Region with two breast cancers reported in the Swedish Cancer Registry, and BC2 diagnosed between 1977 and 2007 were included. Clinical data were abstracted from individual charts and paraffin-embedded tissue collected. We focused on patients with metachronous CBC (⩾3 months between tumours), excluding patients with synchronous CBC, patients with distant metastasis
Tumour characteristics
Patient and tumour characteristics are described in Table 1. Median follow-up time was 11.4 years for patients without breast cancer related death, and 9.1 years in the whole patient cohort. BC2 was generally smaller than BC1 and more often PR-negative. In addition, BC2 was less often treated with radiotherapy, but more often with endocrine therapy. No general difference was seen between BC1 and BC2 in type of surgery used, lymph-node status, TNM-stage, or ER-status. When comparing tumours
Discussion
To our knowledge, this is the largest cohort of CBC-patients with access to detailed patient information, a long follow-up period, as well as tumour-tissue, ever studied. As previously suggested, we found hormone-receptor status within tumour-pairs to be highly correlated [9], [10]. In addition, TNM-stage was correlated between tumours. This may in part be explained by individual patient’s delay in reporting symptoms and compliance to follow-up. Other explanations are genetic and environmental
Financial support
This work was supported by the Swedish Breast Cancer Association (BRO) (2011, 2014); the Skåne University Hospital Foundation (2014-94413); the Percy Falk Foundation (2011); the Swedish Cancer Society (13 0499); the Swedish Research Council (B0262601, 521-2011-3021); the Gunnar Nilsson Cancer Foundation (2013); the Mrs. Berta Kamprad Foundation (13/2013); the Anna and Edwin Bergers Foundation (2014); Skane County Council’s Research and Development Foundation (REGSKANE-434091); and Governmental
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.
Conflict of interest statement
None declared.
Acknowledgements
We want to thank Kristina Lövgren for construction of the TMA and for retrieving tumour paraffin blocks. We also want to thank Gunilla Chebil for locating and collecting paraffin blocks, and Sara Baker for data base construction and collection of paraffin blocks.
In addition we are indebted to the South-Swedish Oncological Centre providing us with data from the Cancer Register, and to the skilled and helpful staff at the surgical, oncological and pathological clinics, and at the medical archives
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