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Metastatic Breast Cancer

Chapter 12 - Breast Cancer in the Senior Patient

Endocrine Therapy

Endocrine therapy is the treatment of choice for women with HR+ and non-life-threatening metastatic disease. In patients with durable response or prolonged disease stabilisation from hormonal therapy, the use of a subsequent line of non-cross-resistant endocrine therapy is considered an adequate strategy at the time of disease progression. Several treatment options are available: tamoxifen, AIs (including a switch from a nonsteroidal to a steroidal AI in the setting of progression), fulvestrant, progestins, and androgens.

Everolimus in combination with exemestane is an active treatment option, but toxicity has to be carefully monitored since more on-treatment deaths in older patients were reported in the BOLERO-2 trial subgroup analysis.

Palbociclib in combination with letrozole (PALOMA 1) or fulvestrant (PALOMA 3) improves PFS in comparison to endocrine treatment alone. This effect is age-independent. The PALOMA-1 trial per age subgroup analysis has reported that the combination of palbociclib + letrozole is well tolerated in older patients (aged ≥ 65 years) despite the higher incidence of grade 3-4 neutropaenia and fatigue.

Chemotherapy

Chemotherapy is the treatment of choice in patients with HR-, endocrine-resistant, or rapidly proliferating disease. Single-agent chemotherapy is generally preferred to combination regimens, as they are usually more toxic and provide, at most, a limited survival gain.

Cytotoxic agents with favourable safety profiles such as weekly taxanes or anthracyclines, liposomal doxorubicin, capecitabine, or vinorelbine are recommended.

Retrospective data suggest that eribulin and weekly nab-paclitaxel are safe and active in older patients. Metronomic chemotherapy combines good tolerability with acceptable activity. Although there are limited data on using polychemotherapy in elderly patients, combination oral chemotherapy (vinorelbine and capecitabine) was effective and well tolerated when assessed in patients older than 70 years with advanced cancers, including breast cancer. Dose reductions and schedule modifications are controversial, but should be considered based on organ reserve, pharmacology, and toxicity. As a general rule, elderly patients have reduced tolerance to treatment and therefore, close monitoring of toxicity is recommended.

Biological Agents

In the absence of cardiac contraindication, trastuzumab can be safely administered to elderly patients with HER2-positive, metastatic breast cancer. In fit patients, concurrent administration of trastuzumab and chemotherapy is recommended. Trastuzumab monotherapy with or without endocrine therapy depending on HR status, is a reasonable option in patients with no life-threatening disease, but are unfit for chemotherapy.

New anti-HER2 agents, i.e. pertuzumab in combination with trastuzumab and taxane, and TDM-1 can be offered to fit elderly patients. In a pre-specified subgroup analysis of PFS according to age (<65, n= 681 vs. ≥ 65 years, n=127) of the CLEOPATRA trial, combination of pertuzumab, trastuzumab, and docetaxel benefitted both age groups, when compared with placebo, trastuzumab and docetaxel. However, diarrhoea, fatigue, asthenia, decreased appetite, vomiting and dysgeusia were reported more frequently in the ≥ 65 years subgroup. In contrast, neutropaenia and febrile neutropaenia were reported less frequently in the older age group (where docetaxel dose and cycles were reduced more frequently).

In the EMILIA trial, T-DM1 significantly prolonged PFS and OS with less toxicity than lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and taxane. This benefit was consistently observed across clinically relevant subgroups, albeit less so among patients aged ≥ 75 years (n=25). When T-DM1 was compared to physician’s chemotherapy of choice (THERESA trial), the PFS benefit was noted across all age groups, including aged ≥75 years. The subgroup study of T-DM1 safety and efficacy in the elderly (KAMILLA trial) showed that the overall incidence of ≥grade 3 adverse events and treatment discontinuations were higher in patients ≥65 years. Although the proportion of T-DM1 associated adverse events was similar across all age groups.

Bevacizumab is active in elderly patients in terms of increased PFS over chemotherapy alone. However, in real practice, complications resulting from bevacizumab are significantly higher than what had been reported in randomised clinical trials.

Bisphosphonates and Denosumab

The use of bisphosphonates and denosumab in patients with metastatic bone lesions is indicated irrespective of age, but with caution in patients with decreased renal function.

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