San Antonio Breast Cancer Symposium (SABCS 2013)

Dr Ring talks to ecancertv at SABCS 2013. The prognosis of a woman with early breast cancer is dependent on both tumour and patient characteristics. Tumour-related prognostic factors, such as stage, grade, and biomarker expression are well-described in the breast cancer literature and remain the focus of considerable ongoing research efforts. However patient-related factors which may influence risks of death from competing causes of mortality or tolerance of adjuvant therapies receive less attention. Risks of death from other causes and likely tolerance of treatment are particularly important considerations in the management of the increasing number of older women who are now presenting with early breast cancer. Chronological age itself may be a useful predictor of these outcomes. However older patients represent a heterogeneous population in terms of co-morbidities, fitness, life expectancy, social situation, cognitive function as well as desire for treatment. Therefore an objective definition of 'biological age' might be a more accurate predictor. Ongoing studies are evaluating whether more extensive assessments, incorporating more domains of a CGA, such as functional status, cognitive function and nutrition add to the predictive model. Any incorporation of such measures into routine clinical practice will require further validation and confirmation of clinical utility. Nonetheless such tools assessing biological age do offer the promise to improve further on the advances made in personalising adjuvant therapies that pathological and molecular tumour characterisation have already achieved. As such it seems likely that assessment of these factors in order to more objectively take into account the risks of death from competing causes of mortality and likely tolerance of treatment will become core components to informed adjuvant treatment decisions in the future.

Dr Ring talks to ecancertv at SABCS 2013 about the 'Add-aspirin trial'. This is a phase III double-blind placebo-controlled randomized trial assessing the addition of aspirin after standard primary therapy in breast cancer and other early stage common solid tumours. The primary outcome will be disease-free survival. Secondary endpoints include overall survival, toxicity, cardiac morbidity and assessment of overall healthcare benefits. Translational work will investigate mechanisms of action and biomarkers for toxicity and treatment efficacy (including PIK3CA mutation status and COX-2 expression). Approximately 3100 patients will be needed to test for a 4% improvement in disease free survival associated with aspirin use.

Dr Niravath talks to ecancertv at SABCS about symptom management and quality of life in metastatic breast cancer Approximately 40,000 women in the US die each year of metastatic breast cancer. Because the disease is incurable at this stage, effective symptom management and preservation of quality of life are paramount for these patients. For those with brain metastases, consideration of cognition, quality of life, and overall survival are extremely important because some subsets of patients with breast cancer metastases to the brain may now enjoy prolonged survival of almost 2 years. For solitary brain metastasis, surgical resection followed by whole brain radiotherapy is known to prolong survival, though the addition of whole brain radiotherapy is associated with significant cognitive impairment and decreased quality of life without clear improvement in overall survival. Stereotactic radiosurgery (SRS) shows promise as a therapeutic option for patients with asymptomatic, smaller brain lesions. SRS, as compared to open surgery, results in improved quality of life. Bone metastasis is another common management dilemma for breast cancer patients. Commonly used bone agents, such as bisphosphonates and RANK ligand inhibitors, are known to decrease bone pain and increase quality of life, as well as reduce skeletal-related events. However, safe and optimal duration of bisphosphonates or RANK ligand inhibitors remains unclear in the metastatic breast cancer population. Finally, we will discuss quality measures for delivering end of life care, trends in the country, and methods for improving end of life care with goals of earlier hospice referrals and less treatments at end of life which lead to hospitalizations or ICU stays.

Prof Barrett-Lee talks to ecancertv to give some of his highlights from the 2013 San Antonio Breast Cancer Symposium (SABCS) on studies looking at oestrogen receptors, arthralgia caused (or not) by aromatase inhibitors, compliance, drug cost, exercise and mutational signatures in breast cancer.

Prof Jack Cuzick talks to ecancertv at SABCS 2013. Taking the breast cancer drug anastrozole for five years reduced the chances of post-menopausal women at high risk of breast cancer developing the disease by 53 per cent compared with women who took a placebo, according to a study presented at SABCS 2103. The results of the IBIS II trial could offer a new option for preventing breast cancer in high risk post-menopausal women which is more effective than tamoxifen and has fewer side-effects.

Prof Adrian Harris talks to ecancertv at SABCS 2013 about his talk on hypoxia metabolism in breast cancer. Hypoxia is recognised to induce a multigene programme mainly via HIF1a and also HIF2a transcription factors. Bioinformatics analysis of multiple gene array data sets in breast cancer showed a core hypoxia response programme of approximately 90 genes associated with poor outcome independent of other factors. This core response was significantly over-expressed in triple receptor negative cancers. The team investigated, by bioinformatic approaches, the expression of 133 key enzymes in metabolism, showing that they were strongly associated with different subtypes of breast cancer, which may help in selection of patients for future intervention studies. Overall, although anti-angiogenic therapy alone is now withdrawn from clinical utility in breast cancer, the massive induction of hypoxic microenvironment and synergy with many other therapeutics, suggests that as new approach using induced essentiality should be reassessed in breast cancer.

Dr Wicha talks to ecancertv at SABCS 2013 about how many cancers, including breast cancer, are driven by cells which display stem cell properties, a fact which has significant clinical implications. Furthermore, the demonstrated role of these cells in mediating tumour metastasis and treatment resistance suggests the need to develop strategies to specifically target cancer stem cell (CSC) populations. Promising new technologies including the isolation and molecular characterization of circulating cancer stem cells may provide the opportunity for real time assessment of the efficacy of CSC targeting agents. A number of agents regulating breast CSCs have entered early phase clinical trials which will determine whether effective targeting of CSCs improves patient outcome.

Dr Bogler talks to ecancertv at SABCS 2013 about male breast cancer. It is estimated that 1% of breast cancer occurs in men: the American Cancer Society estimates 2,240 male breast cancer cases vs 234,580 female cases in 2013 in the US. However, the male disease remains understudied and access to clinical trials for men is lags behind, as will be shown by analysis of grants, papers and trials. Dr Bogler makes the case that by including research on male breast cancer alongside the female disease, and providing direct targeted funds, there is the opportunity to fill important gaps in knowledge. Furthermore, raising awareness and improving trial eligibility has the important potential to improve the outcome for men with breast cancer.

Dr Shapiro talks to ecancertv at SABCS 2013 about the inhibition of poly (ADP-ribose) polymerase (PARP). PARP inhibition results in synthetic lethality in cells that have impaired HR, such as BRCA-deficient cells. In breast cancer, the primary activity of PARP inhibitor monotherapy has been in those cancers arising in BRCA carriers. Inhibition of cell cycle kinases can be used to manipulate the activity of DNA repair pathways, creating exploitable cellular backgrounds that have increased sensitivity to DNA damaging agents. The selectivity of rationally designed combinations for transformed cells will require careful preclinical assessment. Nonetheless, cell cycle and DNA repair pathways are expected to yield multiple new strategies for breast cancer.

Dr Donald Berry talks to ecancertv at SABCS 2013 about the changes in breast cancer mortality in developed countries such as the UK, USA and Japan over the last 50 years, due to screening, improved treatment and changing environmental factors.

Dr Loibl talks to ecancertv at SABCS 2013 about her study "PIK3CA mutation predicts resistance to anti-HER2/chemotherapy in primary HER2-positive/hormone-receptor-positive breast cancer". Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in breast cancer, PIK3CA mutations being the most common. Mutations are frequently found in hot-spots located in the helical and kinase domains (exons 9 and 20). Reported data is discrepant with regard to prognostic or predictive value of PIK3CA mutations especially in HER2 positive breast cancer. The team investigated the frequency and prognostic associations of PIK3CA mutations in HER2 positive and triple negative primary breast cancer treated with neoadjuvant therapy. Patients with PIK3CA mutant HER2 positive / HR negative breast cancer are resistant to chemotherapy and dual anti-HER2 treatment. Other treatment options are needed to be tested in this group.

Dr Fallowfield talks to ecancertv at SABCS 2013 about the psychosocial aspects of breast cancer care. Extraordinary advances have been made in the past 3 decades in breast cancer treatment. More women have greater prospects of cure or lengthier, good quality survival. Advances include:- improved diagnostic and staging procedures, sophisticated onco-plastic surgery, enhanced radiotherapy techniques and targeted systemic therapies. Much more attention has also been paid to cancer care delivery and access to specialist nurses, counsellors, support groups and services provided by breast cancer charities. It is questionable whether or not these considerable improvements in treatment delivery and outcomes have led to comparable, measurable changes in patients' psychosocial, functional and sexual well-being. Just as with the exciting advent of personalised and targeted medicine, we need similar endeavours producing more individualised psychosocial care; communication should be flexible, adapted to the varying needs of individuals, appropriate screening should enable resources, be that counselling, relaxation therapy, yoga, exercise or mindfulness training to be focussed on those at most risk of the unremitting psychosocial dysfunction that compromises healthy survivorship. Spreading scarce supportive services thinly for all irrespective of their risk of poor adjustment, makes as much sense as administering hormone treatment or trastuzumab without information about receptor status.

Dr Perez talks to ecancertv at SABCS 2013 about HER2 positive breast cancer treatment such as trastuzumab, pertuzuamab and multi-gene profiling.

Dr Fowble talks to ecancertv about the role of radiation in the treatment of the axilla in the setting of neoadjuvant chemotherapy for breast cancer. There is considerable controversy regarding the appropriate surgical procedure and its timing for evaluating the status of the axillary nodes in the neoadjuvant setting. Sentinel lymph node (SLN) surgery following initial chemotherapy avoids an axillary dissection and its associated morbidity in clinical N0 patients who have pathologic negative SLN. The potential advantage of neoadjuvant chemotherapy is the ability to adjust surgical and radiation treatment based on pathologic response and thereby minimise the morbidity of combined therapy.

Dr Wrana talks to ecancer at SABCS 2013 about his work looking at exosomes - cell derived vescicles - which affect how cancer cells become mobile, in turn causing cancer metastases. The fibreblast stimulating mobility of tumour cells was examined and exosomes were found to be the main carrier of the signal for movement. This movement signal, known as the 'planar cell polarity signal', has been found to be the main signal involved in the process. If interfered with there is the potential to stop cell mobility and thus metastases; as shown in animal models so far.