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Systemic Treatment of Metastatic Breast Cancer (MBC) in Older Adults
S24
Abstracts / The Breast 36 S1 (2017) S19–S76
unacceptable toxicity (unacceptable should be defined together with the patient) (LoE:1B) [1]. A meta-analysis found that longer (i.e. maintenance) first-line chemotherapy (CT) duration was associated with a substantially longer PFS and a clinically modest but statistically significant improvement in overall survival [3]. In one randomized trial that addressed continuous versus intermittent first-line chemotherapy in conjunction with QoL, the continuous chemotherapy strategy was associated with better QoL [4]. Maintenance therapy may involve single agents or combinations, with options including endocrine therapies, HER2 targeted therapies, cytotoxic agents and biologic therapies. Optimal agents have a low cumulative toxicity. Investigational approaches testing approaches that include biologic agents or immunotherapy may result in new evidence-based approaches for maintenance therapy in future. References [1] [2] [3] [4]
Cardoso F. et al. The Breast 2012; 21: 242–252. Cardoso F. et al. Ann Oncol 2017; 28: 16–33. Gennari A. et al. J Clin Oncol 2011; 29: 2144–2149 Coates A. et al. New Engl J Med 1987: 317: 1490–1495
IN15
tumor characteristics. As the treatment benefit is seen regardless of age group, age alone is not sufficient to determine the type and intensity of treatment. However, it should be kept in mind that agerelated physiological changes are expected to affect various organs and functions. Such changes can subsequently affect certain pharmacokinetic and pharmacodynamics of numerous anticancer drugs, and reduce the ability of organs/systems to withstand the negative effects of drugs. Several age-related factors can influence the management plan in older adults with MBC. Comorbidities can affect treatment tolerability and therefore influence eventual regimen choice and, concurrent medications can have important interactions. Furthermore, cognitive and psychological status can impact strategy understanding and consent, adherence to complex treatment regimens and toxicities management. Nutrition and physical function can influence treatment tolerance and prognosis, and socio-economic factors can also influence adherence to treatment. Hence, older patients warrant explicit monitoring and proactive management of treatment toxicities, which could well match cautious dose escalation strategy especially for vulnerable or frail ones. Despite recent advances in the systemic treatment of ABC, management of older patients is still challenging, given the difficulty of generalizing available treatment regimens to this complex patient group, due mostly to under-representation in many pivotal clinical trials, variable aging trajectory, and lack of data on managing less fit or frail patients.
ORAL DRUGS: CHALLENGES FOR THE ONCOLOGY NURSE C.B. Boers-Doets1 1 CB Boers ORG, Wormer, NL and The Netherlands Leiden University Medical Center, Leiden NL
IN17
Oral drugs – they seemed so easy in use. Actually, despite their advantages, they can be pretty challenging. The benefits are that patients do not need to travel so often to their clinic and spend so much time there – so more freedom. This treatment option has disadvantages too. Patients need to know much more about their treatment than with IV treatment. They need to understand when to take their drugs and how much of the drugs. They need to know if there is interaction with food, drinks, supplements and other drugs. They need to be instructed in what to do when they missed a dose or took too much. They need to understand what consequences treatment delays and dose adjustments have. They are remembered about their cancer more often because oral treatments are taken more often than iv treatments are provided. Another difficult part is the partnership with the healthcare professionals. When does a patient need to contact them? How to act when they didn’t do what they were supposed to do? Oral drugs are quite challenging for all involved parties. Without an interdisciplinary approach oral treatment will not be as effective as it can be. Best results can be achieved when all parties work together, support each other, say the same, explain the same, react the same. In this mini training, I will guide you through the options to consider so both parties will benefit.
Frédérique Penault-Llorca Centre Jean Perrin, Department de Pathology, Clermont Ferrand, France
IN16 SYSTEMIC TREATMENT OF METASTATIC BREAST CANCER (MBC) IN OLDER ADULTS Laura Biganzoli, Julianne Lima, Erica Moretti, Emanuela Risi, Marta Pestrin, Amelia McCartney Istituto Toscano Tumori, Prato Hospital, Medical Oncology Department, Prato, Italy The goal of care in patients with MBC is to optimize the length and quality of life. Treatment decision is based both on patient and
THE BIOLOGY OF INFLAMMATORY BREAST CANCER
Inflammatory breast cancer (IBC) is a rare and aggressive phenotype of breast cancer encompassing approximately 3% of newly diagnosed breast tumors. IBC tends to affect younger women when compared to locally advanced non-IBC with a median age at diagnosis of 57 years. There are considerable geographic/racial disparities. IBC frequency varies between 1% (Western Europe) to 10% (North Africa) and as the highest incidence in AfricanAmerican women and lowest in Asians and Pacific Islanders. IBC has no histological diagnostic criteria and its diagnosis is based primarily on its clinical presentation. In the TNM classification, IBC is classified as T4d. For IBC, although gene expression profiling studies have shown the presence of the same classes of the intrinsic classification of nonIBC, differences do exist in several key pathways and proteins. Half of IBC do not express hormonal receptors, 40% overexpress HER2, and to a lesser extend EGFR. E-Cadherin over expression is a hallmark of IBC, along with p53 mutation and over expression of MUC1. IBC are more frequently classified by molecular subtyping in the HER2 or the basal subtypes and sets of genes can discriminate IBC from non-IBC with discriminator genes associated with cell motility, adhesion and angiogenesis some of them being potential therapeutic targets. Recent comprehensive genomic profiling studies of IBC have revealed up to 96% of clinically relevant genomic alterations. Key molecular differences include significant alterations in the PI3K and JAK/STAT pathways, MYC amplification (42% in the triple negative sub group), elevated aberrations in DNA-repair genes and cell-cycle regulations suggesting of significant genomic instability contributing to treatment resistance. Furthermore, they have confirmed higher rates of HER2 overexpression/amplification with neoadjuvant treatment with trastuzumab resulting in improved outcomes for patients with HER2+ IBC. International efforts have initiated prospective collection of IBC specimens in order to facilitate future tumor tissue and blood-based biomarker studies.
Abstracts / The Breast 36 S1 (2017) S19–S76
unacceptable toxicity (unacceptable should be defined together with the patient) (LoE:1B) [1]. A meta-analysis found that longer (i.e. maintenance) first-line chemotherapy (CT) duration was associated with a substantially longer PFS and a clinically modest but statistically significant improvement in overall survival [3]. In one randomized trial that addressed continuous versus intermittent first-line chemotherapy in conjunction with QoL, the continuous chemotherapy strategy was associated with better QoL [4]. Maintenance therapy may involve single agents or combinations, with options including endocrine therapies, HER2 targeted therapies, cytotoxic agents and biologic therapies. Optimal agents have a low cumulative toxicity. Investigational approaches testing approaches that include biologic agents or immunotherapy may result in new evidence-based approaches for maintenance therapy in future. References [1] [2] [3] [4]
Cardoso F. et al. The Breast 2012; 21: 242–252. Cardoso F. et al. Ann Oncol 2017; 28: 16–33. Gennari A. et al. J Clin Oncol 2011; 29: 2144–2149 Coates A. et al. New Engl J Med 1987: 317: 1490–1495
IN15
tumor characteristics. As the treatment benefit is seen regardless of age group, age alone is not sufficient to determine the type and intensity of treatment. However, it should be kept in mind that agerelated physiological changes are expected to affect various organs and functions. Such changes can subsequently affect certain pharmacokinetic and pharmacodynamics of numerous anticancer drugs, and reduce the ability of organs/systems to withstand the negative effects of drugs. Several age-related factors can influence the management plan in older adults with MBC. Comorbidities can affect treatment tolerability and therefore influence eventual regimen choice and, concurrent medications can have important interactions. Furthermore, cognitive and psychological status can impact strategy understanding and consent, adherence to complex treatment regimens and toxicities management. Nutrition and physical function can influence treatment tolerance and prognosis, and socio-economic factors can also influence adherence to treatment. Hence, older patients warrant explicit monitoring and proactive management of treatment toxicities, which could well match cautious dose escalation strategy especially for vulnerable or frail ones. Despite recent advances in the systemic treatment of ABC, management of older patients is still challenging, given the difficulty of generalizing available treatment regimens to this complex patient group, due mostly to under-representation in many pivotal clinical trials, variable aging trajectory, and lack of data on managing less fit or frail patients.
ORAL DRUGS: CHALLENGES FOR THE ONCOLOGY NURSE C.B. Boers-Doets1 1 CB Boers ORG, Wormer, NL and The Netherlands Leiden University Medical Center, Leiden NL
IN17
Oral drugs – they seemed so easy in use. Actually, despite their advantages, they can be pretty challenging. The benefits are that patients do not need to travel so often to their clinic and spend so much time there – so more freedom. This treatment option has disadvantages too. Patients need to know much more about their treatment than with IV treatment. They need to understand when to take their drugs and how much of the drugs. They need to know if there is interaction with food, drinks, supplements and other drugs. They need to be instructed in what to do when they missed a dose or took too much. They need to understand what consequences treatment delays and dose adjustments have. They are remembered about their cancer more often because oral treatments are taken more often than iv treatments are provided. Another difficult part is the partnership with the healthcare professionals. When does a patient need to contact them? How to act when they didn’t do what they were supposed to do? Oral drugs are quite challenging for all involved parties. Without an interdisciplinary approach oral treatment will not be as effective as it can be. Best results can be achieved when all parties work together, support each other, say the same, explain the same, react the same. In this mini training, I will guide you through the options to consider so both parties will benefit.
Frédérique Penault-Llorca Centre Jean Perrin, Department de Pathology, Clermont Ferrand, France
IN16 SYSTEMIC TREATMENT OF METASTATIC BREAST CANCER (MBC) IN OLDER ADULTS Laura Biganzoli, Julianne Lima, Erica Moretti, Emanuela Risi, Marta Pestrin, Amelia McCartney Istituto Toscano Tumori, Prato Hospital, Medical Oncology Department, Prato, Italy The goal of care in patients with MBC is to optimize the length and quality of life. Treatment decision is based both on patient and
THE BIOLOGY OF INFLAMMATORY BREAST CANCER
Inflammatory breast cancer (IBC) is a rare and aggressive phenotype of breast cancer encompassing approximately 3% of newly diagnosed breast tumors. IBC tends to affect younger women when compared to locally advanced non-IBC with a median age at diagnosis of 57 years. There are considerable geographic/racial disparities. IBC frequency varies between 1% (Western Europe) to 10% (North Africa) and as the highest incidence in AfricanAmerican women and lowest in Asians and Pacific Islanders. IBC has no histological diagnostic criteria and its diagnosis is based primarily on its clinical presentation. In the TNM classification, IBC is classified as T4d. For IBC, although gene expression profiling studies have shown the presence of the same classes of the intrinsic classification of nonIBC, differences do exist in several key pathways and proteins. Half of IBC do not express hormonal receptors, 40% overexpress HER2, and to a lesser extend EGFR. E-Cadherin over expression is a hallmark of IBC, along with p53 mutation and over expression of MUC1. IBC are more frequently classified by molecular subtyping in the HER2 or the basal subtypes and sets of genes can discriminate IBC from non-IBC with discriminator genes associated with cell motility, adhesion and angiogenesis some of them being potential therapeutic targets. Recent comprehensive genomic profiling studies of IBC have revealed up to 96% of clinically relevant genomic alterations. Key molecular differences include significant alterations in the PI3K and JAK/STAT pathways, MYC amplification (42% in the triple negative sub group), elevated aberrations in DNA-repair genes and cell-cycle regulations suggesting of significant genomic instability contributing to treatment resistance. Furthermore, they have confirmed higher rates of HER2 overexpression/amplification with neoadjuvant treatment with trastuzumab resulting in improved outcomes for patients with HER2+ IBC. International efforts have initiated prospective collection of IBC specimens in order to facilitate future tumor tissue and blood-based biomarker studies.