1st UK Interdisciplinary Breast Cancer Symposium Manchester January 2018 Some Musings

POETIC Trial Multicentre, phase III, randomised trial for post menopausal women with ER/PR positive invasive breast cancer to determine whether 2 weeks of perioperative aromatase inhibitor before and after surgery improves outcome. Diagnostic core biopsy compared with surgical specimen particularly for Ki67

POETIC Trial Primary outcome – time to recurrence Slight numerical advantage, but not statistically significant Prognostic information on change in Ki67

POETIC Trial Ki67 High Low 19% 9% 4% Diagnostic Core Operative Core Recurrence Rate High 19% Low 9% 4%

POSH Study Over 3000 women recruited between 2000 and 2008 who were 40 or younger at diagnosis of breast cancer. Prospective cohort study – no interventions

POSH Study Weight -54% healthy, 27% overweight, 19% obese Obese more likely to have a larger cancer, a grade 3 cancer and nodal spread. 66% had no family history of breast cancer

POSH Study Most Gene tested. 201 (8%) BRCA1 mutation 2,396 (88%) No mutation

POSH Study Median 8.2 year follow-up No difference in survival between gene carriers and non gene carriers at any time point Irrespective of whether had bilateral mastectomy (21 gene carriers and 10 non gene carriers) Slight benefit in survival for gene carriers who are triple negative

OlympiAD Trial PARP inhibitor - olaparib 300 women with advanced breast cancer and BRCA mutations, HER2 negative Either olaparib orally or standard chemotherapy Olaparib reduced the risk of progression by 42%, delaying progression by 3 months

Miscellaneous FACE trial – Letrozole no better than Anastrozole 22% of non gene carriers have a deficiency in BRCA (somatic not germline) Have BRCA like phenotype behaviour 40% of breast cancers are obesity related Gut microbiome is important for response to immunotherapy

REACT Trial Randomised to have COX 2 inhibitor –Celocoxib or placebo 2500 patients, 450 events No difference between two groups

Risk reduction- Jack Cuzick Half risk of cancer by losing 10kg if obese 19% of cancers caused by smoking Relative risk reduction for low dose aspirin: 0.6 colorectal cancer 0.9 breast cancer 0.5 oesophageal cancer 0.85 prostate cancer IBIS I tamoxifen treat 59 women to prevent one breast cancer at 10 years. SNPs becoming more important Tyrer-Cuzick version 8 – free download

Generations Study - Swerdlow 100,000 women, 40 year follow-up Lots of blood samples and questionnaires 6000 had breast cancer before they started 2500 have developed it after joining Age at thelarche more important tham menarche Risk of DXT (Hodgkins) 5x higher risk if given within 6 months of menarche rather than within 10 years HRT (uses actual usage rather than current like other studies) No risk for oestrogen only. 2.7x for 10 years of combined HRT.

Gene testing Royal Marsden in new breast cancers Criteria: <=40 <= 45 with first degree relative Bilateral, both < 60 Triple negative any age Breast cancer and ovarian Male Gives 10.8 % BRCA positive rate Clinicians order the gene testing after some training

Lobular Cancer Invasive lobular cancer is the 6th most common cancer in women similar rate as Myeloma or Hodgkins 94% ER positive, associated with HRT usage 14% PTEN mutation (3% for IDC) FGFR4 looking to be a promising target Long term prognosis worse, but only after 5 years

Pre-op MRI Prof Ulrich Bick Radiologist Berlin Breast Cancer Res Treat. 2017 Sep;165(2):273-283. doi: 10.1007/s10549-017-4324-3. Epub 2017 Jun 6. Meta-analysis of pre-operative magnetic resonance imaging (MRI) and surgical treatment for breast cancer. Houssami N1, Turner RM2, Morrow M3. Pre-op MRI Prof Ulrich Bick Radiologist Berlin CONCLUSIONS: Pre-operative MRI is associated with increased odds of receiving ipsilateral mastectomy OR 1.39 and contralateral prophylactic mastectomy OR 1.91 as surgical treatment in newly diagnosed BC patients. No effect on rates of re-excision, re-operation or positive margins. _______________________________________________________________________ Br J Surg. 2015 Jul;102(8):883-93. doi: 10.1002/bjs.9797. Epub 2015 Apr 28. Meta-analysis of the effect of preoperative breast MRI on the surgical management of ductal carcinoma in situ. Fancellu A1, Turner RM2, Dixon JM3, Pinna A1, Cottu P1, Houssami N4. CONCLUSION: Preoperative MRI in women with DCIS is not associated with improvement in surgical outcomes. Mastectomy rates not changed by MR.

Pre-op MRI Prognosis is based on Metastases not local disease Very low local recurrence rates anyway Specificity for MRI is very low for <5mm lesions MRI can’t reliably differentiate between relevant and non-relevant disease – picks up a higher % of low grade cancers

Pre-op MRI Canadian study 2015 JAMA Arnaout et al MR increases risk of: Post diagnostic imaging OR 2.09 Post diagnostic biopsies OR 1.74 Post diagnostic staging OR 1.51 Mastectomy OR 1.73 Contralateral mastectomy OR 1.48 Greater than 30 day wait for surgery OR 2.52