Overcoming the challenges of endocrine therapy for breast cancer

Chanda Warren, who was diagnosed with invasive lobular breast cancer at the age of 45, describes being a breast cancer patient as similar to being a marathon runner. For Chanda, every stage of her journey was a marathon – receiving the diagnosis, having surgery, going through chemotherapy and radiation, then reconstruction. And after all of that, she entered the longest, and what can often be the most difficult, marathon – being on endocrine therapy. This is the time when so many patients aren’t making it to the finish line, because these treatments can be so disruptive and life changing. 

As the most common cancer type for women in New Zealand, 3,300 women will be diagnosed with breast cancer this year. Around 70 percent of early breast cancers are oestrogen receptor positive (ER+) and/or progesterone receptor positive (PR+) and will require treatment to either lower the levels of oestrogen or progesterone, or block their effects.

Endocrine therapies are commonly recommended to target this pathway, reducing the risk of cancer recurrence and the risk of developing secondary breast cancer. 

Tamoxifen has long been used as adjuvant therapy and is effective in both premenopausal and postmenopausal women. Aromatase inhibitors (AIs) are only effective for women already in, or induced into, a postmenopausal state as they reduce non-ovarian production of oestrogen. Three AIs are currently available in New Zealand - anastrozole, letrozole, and exemestane.

The risk of recurrence for hormone sensitive breast cancer is stretched over 20 years. Studies suggest that 10 years of endocrine therapy will be most effective for patients with higher-risk tumours (higher grade and/or lymph node positive). There is consensus in New Zealand that after five years, all patients with hormone-sensitive breast cancer should discuss with their surgeon or oncologist the potential benefits and risks of continuing therapy out to 10 years. 

While endocrine therapies remain the most effective and least toxic treatment for ER+ and PR+ breast cancer, they do pose challenges for patients that GPs can help to overcome. It’s troubling to see studies showing around half of patients discontinue hormonal treatments, often while their risk of recurrence is greatest. 

Common side effects of endocrine therapy include arthralgias, hot flushes, mood changes, fatigue, vaginal dryness/discharge, and nausea. AIs can decrease bone mineral density, so the monitoring of bone density is recommended for those at risk of osteoporosis. Rarer side effects of tamoxifen can include deep vein thrombosis, pulmonary embolus and endometrial cancer.

Many of these side effects can be managed with drugs or supportive care. For hot flushes, drugs like escitalopram, citalopram, venlafaxine, gabapentin and oxybutynin can benefit, while there is some mixed data for acupuncture. Exercise and stretching (through yoga and Pilates, for example) can help to reduce arthralgias. Topical vaginal estriol can relieve urogenital atrophy symptoms. Bone mineral density loss can be prevented by bisphosphonates, which has the dual benefit of reducing the risk of breast cancer recurrence and breast cancer-specific mortality in postmenopausal patients. 

AIs are somewhat more effective than tamoxifen, but they do cause more musculoskeletal toxicity and urogenital atrophy symptoms, making them harder to tolerate. AIs are typically prescribed first, depending on the breast cancer features, and switching to tamoxifen can be a way to encourage adherence. In pre-menopausal women AIs must be given with ovarian function suppression or ovarian function ablation. 

There is growing recognition in New Zealand that GPs should be involved in all stages of breast cancer care. A recent survey by Breast Cancer Foundation NZ of women aged 45 and older showed almost half of respondents (49 percent) said their GP had discussed breast health with them. I believe GPs in particular can play a major part in encouraging patients to stay the course of endocrine therapy and provide symptomatic management for side effects. It’s important to stress the significant role hormone therapies have in breast cancer recurrence risk reduction. Although adherence to endocrine therapies can be hugely challenging for patients, for most who are recommended to take endocrine therapies for breast cancer, the benefits of treatment outweigh the risks. 

October is Breast Cancer Awareness Month and there are loads of different ways to get involved – from being breast-aware, to helping to raise vital funds for Breast Cancer Foundation NZ’s work in research, education and support. Visit breastcancerfoundation.org.nz to learn more.