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Title: Risk assessment of contralateral breast cancer in high-risk patients and formulation of clinical guidelines
Author: Basu, Narendra Nath
ISNI:       0000 0004 5990 4717
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2016
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This thesis assesses the main risk factors contributing to contralateral breast cancer(CBC) amongst high-risk breast cancer patients with a view to formulating clinicallyuseful guidelines. The work has focused on several keys areas; a literature review ofthe various factors contributing to CBC, changing trends towards increasingnumbers of contralateral risk-reducing mastectomies (CRRMs), internationalvariations amongst breast surgeons’ attitudes towards risk-reducing mastectomy(RRM), attitudes towards CRRM amongst UK breast and plastic surgeons,assessment of CBC risk amongst BRCA1/2 mutation carriers and finally theformation of the ‘Manchester Guidelines for CRRM’.Breast cancer patients harbouring mutations in high penetrance genes (i.e. BRCA1/2,TP53, CHEK2, PALB) have the highest risk of developing breast cancer. A positivefamily history also increases the risk of subsequent breast cancer, with not muchevidence to support variation in risk with histological type. Risk reducing strategiesinclude anti-endocrine treatment, risk-reducing bilateral salpingo-oophorectomy(RRBSO) and CRRM with the former likely to account for the global trend ofdecreasing rates of CBC.Over the last decade, rates of CRRM have trebled in the USA – such a clear trendhas not yet been confirmed in Europe. Factors driving this trend include young ageat diagnosis, histological type (lobular carcinoma, lobular carcinoma in situ [LCIS]and ductal carcinoma in situ [DCIS]) and female surgeons. A direct comparison(USA v 4 European countries) found that American surgeons overall had a greaterknowledge of cancer genetics and nearly all (including Dutch and British surgeons)had positive attitudes towards RRM.A proportion of British surgeons were quoting inaccurate levels of CBC risk to theirpatients. Practices in the UK varied regarding CRRM – only 58% of surgeons alwaysdiscussed these cases in the MDT, with less than a third ever seeking apsychological or formal genetic assessment. Surgeons primarily offered thisprocedure to high-risk patients (gene mutation carriers or positive family history)but felt that the main reason patients requested CRRM was to alleviate anxiety. Studying over 1000 breast cancer patients who also had a mutation in either BRCA1or BRCA2 gene revealed that the risk of CBC was approximately 2-3% per year, forat least 2 decades. Young age at first breast cancer development (<40 years) affectedthis risk most. The effect bilateral risk-reducing salpingo-oophorectomy (BRRSO)was initially significant in an unadjusted analysis, but when accounting for delayedentry BRRSO did not appear to affect CBC risk. The use of SNPs was not able tostratify risk of CBC further. By considering the above, the Manchester Guidelines for CRRM have beenformulated. This 5-step protocol allows clinicians to objectively assess the risk ofCBC based on the evidence base and makes suggestions of a multi-disciplinaryapproach to managing requests for CRRM. Several breast units in the UK havealready adopted these guidelines and future studies hope to validate them so thatthey can be used more widely.
Supervisor: Howell, Anthony ; Evans, Gareth Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: breast cancer ; contralateral ; BRCA