SABCS 2016

Prof Richard Finn (University of California, Los Angeles, USA) chairs an expert discussion on the latest in CDK inhibition in breast cancer for ecancertv at SABCS 2016 in San Antonio with Professor Michael Gnant (Medizinischen Universität Wien, Vienna, Austria), Dr Mark Harries (Guy’s & St Thomas’ Hospitals NHS Foundation Trust, UK) and Prof Sandra Swain (Georgetown University Medical Center, Washington, DC, USA) 15 years after the Nobel Prize in Physiology was awarded for the identification of the role of CDK in regulating the cell cycle, 2016 has seen some of the most exciting advances for the actual and potential clinical utility of this research for breast cancer patients. The panel first discussed Phase III data from this year, including the ribociclib MONALEESA-2 trial and the ‘stunning’ results seen for palbociclib in the PALOMA-2 and PALOMA-3 trials. With regards to the toxicity profiles even though neutropenia was noted, it was suggested that these treatments remain a ‘paradigm shift’, as some patients remain on treatment for ‘10 months longer than endocrine therapy’. Another treatment looking at CDK 4/6 inhibition is abemaciclib, which has been shown to cause less neutropenia than the other treatments, but increased diarrhoea. The panel suggest this could be due to the increased activity against CDK4 and therefore gastrointestinal issues. The international panel confirmed that the optimism for the use of these treatments was seen in both US and Europe, due to the ‘magnitude of benefit’ seen. Some unresolved questions were posed, such as how the treatments are being sequenced and the use of them in the early breast cancer setting. Hoping to help answer this question is the PALLAS trial, which is evaluating the addition of 2 years of palbociclib to standard adjuvant endocrine therapy for patients with HR / HER2- early breast cancer (EBC). The panel then briefly touched on biomarkers, the use of CDK 4/6 inhibitors outside of ER BC, and the strength of PFS and time to chemotherapy as endpoints verses OS. It is clear that the significance of CDK 4/6 inhibition in breast cancer will continue to grow, with the importance of continuing medical education highlighted so that this breakthrough in the treatment of breast cancer can be appropriately managed.

Dr Hurvitz presents data at San Antonio Breast Cancer Symposium 2016 from the phase II neoMONARCH trial of abemaciclib, a CDK4/6 inhibitor, as a single agent or combined with anastrozole for post-menopausal women with HR , HER- breast cancer. The study found that, alone or with anastrozole, abemaciclib induced significantly greater cell cycle arrest, defined by reduced Ki67 expression.

Dr Mamounas presents data at the San Antonio Breast Cancer Symposium 2016 about the impact of letrozole treatment up to, and beyond, 5 years on disease free survival of post-menopausal women with HR breast cancer who have completed previous adjuvant aromatase inhibitory therapy. From nearly 4000 patients enrolled, he describes a reduction in the that of distant recurrent disease and improvement in breast cancer free interval events, though notes that overall benefits on DFS did not meet statistical significance. Dr Mamounas also notes an elevated risk of thrombotic events after 2.5 for patients receiving letrozole past that point.

Dr Kornblum presents results at the San Antonio Breast Cancer Symposium 2016 from a randomised, double-blind phase II trial of everolimus vs placebo in combination with fulvestrant from HR /HER- metastatic breast cancer for patients resistant of aromatase inhibitor therapy. The addition of everolimus doubled median PFS to 10.4 months, with adverse events at a higher, but manageable, severity, consistent with previous assessment of everolimus in the BOLERO-2 trial.

Prof Linn presents data at the 2016 San Antonio Breast Cancer Symposium from the TEAM IIb trial, in which post-menopausal women with hormone receptor positive breast cancer, with no metastases, were treated with 3 years of adjuvant bisphosphonate therapy. She describes no proof of statisically significant benefit of 3 years of ibandronate, with a slight increase in gastrointestinal side effects, and non-significant trend towards improved disease free survival and reduced bone metastases.

Dr O'Regan presents data at the 2016 San Antonio Breast Cancer Symposium from the BELLE-3 trial of buparlisib and fulvestrant for post-menopausal women with locally advanced or metastatic breast cancer who have progressed after mTOR inhibitory therapy. With a primary endpoint of improved progression-free survival, and secondary endpoints of assessing risk through PIK3CA expression, she describes this trial as a success, but notes a slight incidence of psychological effects on a minority of patients, which may be due to the small size of buparlisib permitting it to cross the blood brain barrier.

Dr Cohen presents analysis at the San Antonio Breast Cancer Symposium 2016 of primary and metastatic breast cancer biopsies, with samples matched where available, which underwent whole exome sequencing and transcriptome sequencing to give a clearer view of tumour evolution. He highlights notable acquired mutations in ER positive MBC, which may inform treatment choice for patients and target choice for future research.

Dr Han presents results at the San Antonio Breast Cancer Symposium 2016 from a randomised phase II study of veliparib against placebo in combination with carboplatin and paclitaxel, for patients with locally recurrent of metastatic BRCA1/2 mutated breast cancer. The data presented at this press conference reflects two arms of a three arm study, with the veliparib plus temozolomide results not yet available. Dr Han describes the addition of veliparib as well tolerated, with similar toxicity profile to the placebo arm, and notes an improvement in partial r response rate, though clinical benefit and duration of response was equivalent to placebo.

Dr O'Regan speaks with ecancertv at SABCS 2016 about the outcomes of the phase III BELLE-3 trial, in which post-menopausal women with advanced or metastatic HR positive breast cancer who had disease progression during or after mTOR inhibitor therapy were treated with buparlisib and fulvestrant. While the combination improved progression free survival at 6 months, as gauged by PIK3CA status, she notes the dose reductions and adverse events among a small number of patients in the trial, including incidences of depression and suicidal ideation.

Dr Mamounas speaks with ecancertv at SABCS 2016 about the impact of letrozole treatment up to, and beyond, 5 years on disease free survival of post-menopausal women with HR positive breast cancer who have completed previous adjuvant aromatase inhibitory therapy. From nearly 4000 patients enrolled, he describes a reduction in the that of distant recurrent disease and improvement in breast cancer free interval events, though notes that overall benefits on DFS did not meet statistical significance. Dr Mamounas also notes an elevated risk of thrombotic events after 2.5 for patients receiving letrozole past that point.

Dr Kaklamani speaks with ecancertv at SABCS 2016, reviewing the mornings press release session which she chaired. She highlights the work of Dr Terry Mamounas and Dr Ofir Cohen.

Dr Tolaney speaks with ecancertv at the 2016 San Antonio Breast Cancer Symposium about results from a phase Ib/II study of anti-PD-1 pembrolizumab with eribulin mesylate, a microtubule growth inhibitor, for metastatic breast cancer patients. She describes the benefits to patients, with a complete and objective responses recorded at this interim analysis, which she notes as being independent of PD-L1 positivity in samples. Dr Tolaney considers the toxicity profile of checkpoint inhibitory therapy, and the broader future of immunotherapy for breast cancer.

Dr Smith speaks with ecancertv at the 2016 San Antonio Breast Cancer Symposium about results from the IBIS-1 trial of tamoxifen as a chemopreventive treatment for women at higher risk of developing breast cancer. He notes a significant rate of discontinuation of therapy from women experiencing natural symptoms of menopause, which might be mistaken for side effects of the tamoxifen. Dr Smith considers room for improvement communication to clarify potential outcomes and risks for trial patients.

Dr Couch speaks with ecancertv at SABCS 2016 about establishing risks associated with a variety of genes thought to influence breast cancer prognosis. He describes genes identified from over 60,000 patients which, by their presence or absence, can modulate the lifetime likelihood of developing breast cancer, including evidence towards suspected risk-promoting genes being statistically unlikely to increase chances.

Dr Vinnedge speaks with ecancertv at SABCS 2016 the function of the DEK protein in regulation of gene expression, and the upregulation of tumourigenic signalling through Wnt pathways. She describes the influence of DEK expression on macrophage behaviour, resulting in angiogenesis, immune suppression, and iron recycling to promote local cell growth.

Dr Pizot speaks with ecancertv at the 2016 San Antonio Breast Cancer Symposium to discuss her research into breast cancer trends globally. She describes an overall global trend in reduced mortality, with significant reductions in England and Wales, but notes Latin America and South Korea as regions which have seen increases, and considers the societal drivers behind these outliers.

Dr Kornblum speaks with ecancer at the San Antonio Breast Cancer Symposium 2016 about results from the PrECOG 0102 trial, a randomised, double-blind phase II trial of everolimus vs placebo in combination with fulvestrant from HR /HER- metastatic breast cancer for patients resistant of aromatase inhibitor therapy. He describes that the addition of everolimus doubled median PFS to 10.4 months, with adverse events at a higher, but manageable, severity, consistent with previous assessment of everolimus in the BOLERO-2 trial.

Dr Hurvitz speaks with ecancertv at SABCS 2016 about the outcomes of the neoMONARCH trial of abemaciclib, a CDK 4/6 inhibitor, in combination with anastrozole for women with HR positive breast cancer. The study found that, alone or with anastrozole, abemaciclib induced significantly greater cell cycle arrest, defined by reduced Ki67 expression.

Dr Eljertsen speaks with ecancertv at SABCS 2016 about a trial regimen for the treatment of early breast cancer, of 3 cycles of epirubicin and cyclophosphamide (EC) before 3 cycles of docetaxel and cyclophosphamide (CD), compared to 6 cycles of the latter. He describes the addition of anthracyclin treatment as having no clinical benefit for patients with a non-mutated TOP2 gene, resulting only in increased toxicity. Given that Dr Eljertsen estimates only 15% of tumours express a TOP2a mutation, added anthracyclin treatment ought to be deferred in the majority of patients.

Prof Linn speaks with ecancertv at SABCS 2016 to discuss the impact of adjuvant bisphosphonate therapy on patients with early stage breast cancer, finding that there was no significant improvement through its addition after 3 years follow up. Weighing the slight trends of gastrointestinal side effects against lowered risk of bone metastases, Prof Linn considers if 3 years is an adequate follow up to see the full effects of added bisphosphonate therapy, and notes patient concerns over osteonecrosis of the jaw as a side effect of treatment.

Dr Rimawi speaks with ecancertv at SABCS 2016 about the results of a trial in which neoadjuvant TCHP chemotherapy was administered alongside oestrogen deprivation therapy in HR/HER positive breast cancer patients. He considers comments that the chemotherapy regimen seems to blunt the clinical benefit of anti-oestrogens, which may in turn be attributable to the sheer success of chemotherapy, or be influenced by the timing and dosage of the regimens.

Dr Nangia speaks with ecancertv at SABCS 2016 about a cooling cap system which can prevent hair loss for women undergoing chemotherapy. She describes the rates of hair retention, noting that thinning is still likely even in patients who retain their hair, and highlights the safety for using the system in treating breast cancer compared to haematological disease, in which vasoconstriction might increase scalp metastases due to circulating tumour cells.

Dr Rimawi presents data at SABCS 2016 about the influence of added oestrogen deprivation to neo-adjuvant chemotherapy to with HR/HER2 positive breast cancer patients. Overall, he describes additional therapy as not producing clinically significant results, which could be attributed to the chemotherapy regimen 'blunting' the clinical benefit of anti-oestrogens. For more from this trial, Dr Rimawi spoke with ecancer, with a video interview coming soon.

Dr Han speaks with ecancertv at SABCS 2016 about the outcomes from a trial of added velaparib to chemotherapy for BRCA1/2 mutant metastatic breast cancers. Compared to carboplatin and paclitaxel, she describes the addition of velaparib as extending progression free survival, though not to a statistically significant extent, with no additional toxicity.

Dr Cohen speaks with ecancertv at SABCS 2016 about the lessons learned from sequencing of the whole exome and transcriptome of metastatic breast cancer. The insight in tumour evolution from primary lesions to metastatic cases highlights potential targets for personalised therapy, and forms a better understanding of molecular and metabolic pathways most highly regulated in cancer cells.