Endocrine therapy remains a cornerstone of care in HR+/HER2- early-stage breast cancer, but treatment-related adverse events (AEs) and nonadherence can limit its benefit. It is important to educate patients on the various available endocrine therapies and their AEs before treatment initiation to limit nonadherence.

The endocrine therapies we talk about with our patients who have HR+/HER2- early-stage breast cancer are SERMs such as tamoxifen; aromatase inhibitors such as anastrozole; and, for premenopausal patients, GnRH agonists such as goserelin. We can also give CDK4/6 inhibitors such as ribociclib or abemaciclib in patients who have a higher risk of recurrence, and sometimes we give bone-modifying agents for the treatment of AEs such as osteopenia and osteoporosis.

One limitation of endocrine therapies is adherence. In early-stage breast cancer, not all patients adhere to treatment. Of course, a medication is not going to work if a patient does not take it, so it is crucial that we take the time to discuss the benefits of endocrine therapy, along with any potential AEs, emphasizing the fact that we can overcome many of these AEs through careful disease management.

One way to address AEs is to alter dosing. For example, with tamoxifen, I have found that breaking up the once-daily 20-mg dose into twice-daily 10-mg doses helps some patients feel better. Sometimes altering the time that a medication is taken can also make for an easier schedule and can reduce the occurrence of unpleasant AEs (eg, hot flashes) during the day. Unfortunately, for some therapies, we only have 1 dose level, which becomes a limitation, and this is true for aromatase inhibitors.

Ultimately, what is important is that patients understand the need to communicate any side effects they may be experiencing because there are ways that we can help them. Oddly enough, despite all the communication systems that we currently have in place, communication between a physician and a patient has actually become harder. For example, patients can no longer make a direct phone call to their physician; it has to go through electronic messaging systems and other people who answer patient calls, which is discouraging for patients. In the future, I hope that we will adopt more digital tools because they have really empowered patients.

Before initiating a course of endocrine therapy, it is important to have a good conversation with the patient, as the mindset of the patient at the start of treatment can dictate treatment outcomes. During these discussions, it is important to highlight the benefits of treatment (eg, relapse risk reduction and survival improvement) and address any potential treatment-related AEs. It is difficult to predict up front which patients will experience specific AEs, which is why the partnership between the patient and the clinical team is important. The team is there to problem solve and troubleshoot when patients experience these AEs.

Some of the more common side effects that can lead to nonadherence in patients on endocrine therapy include arthralgia, stiffness, and joint discomfort from aromatase inhibitors, as well as vasomotor symptoms such as hot flashes and insomnia that may occur with a number of endocrine therapies. Other side effects, such as vaginal dryness and sexual dysfunction, can also be problematic for patients and their relationships.

For me, if a patient who is being treated with the aromatase inhibitor anastrozole comes back with severe symptoms 6 or 8 weeks after treatment initiation, I would talk to them about switching to another aromatase inhibitor. I may first suggest that they take a break from anastrozole, let those symptoms wash out, and then start a trial of exemestane. If the symptoms recur, we then talk about switching from an aromatase inhibitor to tamoxifen because we would prefer to have the patient on some sort of endocrine therapy rather than nothing at all.

Looking to the future, I agree with Dr Kaklamani regarding digital tools. Several trials have shown how capturing a patient’s reported symptoms in real time often results in early intervention and can really improve a patient’s quality of life. Currently, although there are a lot of barriers to “rolling this out” more broadly, I think that the data are very impressive.

I think that we have all developed a “bag of tricks” for helping patients deal with endocrine therapy–related toxicities. For one, bone stiffness can be a huge problem. Randomized trials have shown that exercise can help mitigate musculoskeletal symptoms. Additionally, SNRIs have been shown to relieve arthralgia (ie, duloxetine) and vasomotor symptoms (ie, venlafaxine and oxybutynin). There is also a new class of drugs, neurokinin receptor antagonists, that can be particularly beneficial for patients with breast cancer. All these tools, I think, have helped significantly with ensuring treatment adherence.

One issue is that we do not always know how adherent a patient is to their therapy. If a patient says, “I have been on tamoxifen for 1 month, and I cannot sleep because I am having hot flashes at night,” we can intervene. However, the data show that many patients gradually decrease their adherence or stop taking their medication altogether, but they will not bring it up during a visit.

I think that not assessing adherence on a regular basis is a big reason we are missing nonadherence and not intervening when we can. Just focusing on toxicity is not enough. Data show that there are other reasons patients do not take their endocrine therapy as prescribed. For example, cost is one of the biggest barriers to adherence, and reducing costs consistently shows significant impacts on promoting treatment adherence. There are a lot of things that we can do in terms of monitoring for adherence, and I think that if we are intentional about it, we can hopefully reduce treatment discontinuation rates over time.