Manchester January 2018 Some Musings POETIC Trial Multicentre phase III randomised trial for post menopausal women with ERPR positive invasive breast cancer to determine whether 2 weeks of perioperative aromatase inhibitor before and after surgery improves outcome ID: 931039
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Slide1
1st UK Interdisciplinary Breast Cancer Symposium
Manchester January 2018
Some Musings
Slide2POETIC 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
c
ore biopsy compared with surgical specimen particularly for Ki67
Slide3POETIC Trial
Primary outcome – time to recurrence
Slight numerical advantage, but not
statistically significant
Prognostic information on change in Ki67
Slide4POETIC Trial
Ki67
Diagnostic Core
Operative Core
Recurrence Rate
High
High
19%
High
Low
9%
Low
Low
4%
Slide5POSH Study
Over 3000 women recruited between 2000 and 2008 who were 40 or younger at diagnosis of breast cancer.
Prospective cohort study – no interventions
Slide6POSH 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
Slide7POSH Study
Most Gene tested.
201 (8%) BRCA1 mutation
136 (4%) BRCA2 mutation
2,396 (88%) No mutation
Slide8POSH 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
Slide9OlympiAD 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
Slide10Miscellaneous
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
Slide11REACT Trial
Randomised to have COX 2 inhibitor –
Celocoxib
or placebo
2500 patients, 450 events
No difference between two groups
Slide12Risk 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
Slide13Generations 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.
Slide14Gene 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
Slide15Lobular Cancer
Invasive lobular cancer is the 6
th
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
Slide16Breast 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
N
1
,
Turner RM
2
,
Morrow M
3
.
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
A
1
,
Turner RM
2
, 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
Prof Ulrich Bick
Radiologist Berlin
Slide17Prognosis is based on Metastases not local diseaseVery low local recurrence rates anywaySpecificity 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
Slide18Pre-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