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The Pharmacist and Patients With HER2-Positive or HER2-Low Metastatic Breast Cancer: Navigating the Treatment Landscape

The Pharmacist and Patients With HER2-Positive or HER2-Low Metastatic Breast Cancer: Navigating the Treatment Landscape - Breast Cancer
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The most commonly diagnosed cancer in women is breast cancer, with most cases diagnosed at an early stage.1 Advanced, or metastatic breast cancer (MBC) remains incurable, but it is treatable.1 Due to its heterogeneous nature, individual treatment management is necessary.1 Breast cancer can be classified according to hormone receptor expression and human epidermal growth factor receptor 2 (HER2) gene amplification/gene overexpression, which are used to guide treatment decisions and to determine patient prognosis.1 HER2-positive breast cancer is defined as having HER2 expression 3+ by immunohistochemistry (IHC) or if it has an IHC score of 2+ with HER2 gene amplification tested by in situ hybridization (ISH).1 Treatments include the monoclonal antibodies margetuximab, pertuzumab, and trastuzumab; antibody–drug conjugates (ADCs) ado-trastuzumab emtansine and fam-trastuzumab deruxtecan-nxki (T-DXd); and tyrosine kinase inhibitors lapatinib, neratinib, or tucatinib.2

A recent change in HER2 breast cancer scoring defined a new classification: HER2-low.2 HER2-low is defined as breast cancer with an IHC score of 1+ or 2+/ISH-negative.2 Although previously considered difficult to treat, recent clinical trials had success with treatment of HER2-low breast cancer with ADCs.2 The phase 3 DESTINY-Breast04 clinical trial demonstrated that T-DXd significantly improved survival in patients with advanced HER2-low breast cancer when compared with chemotherapy.2 This led to the Food and Drug Administration approval of T-DXd for treatment in patients with metastatic or unresectable HER2-low breast cancer in August 2022.2

Pharmacists are at the forefront of treatment of MBC and conveying timely medication information to patients and their healthcare team. Patients often encounter barriers to treatment due to health insurance issues and intolerable side effects. To mitigate these barriers, pharmacists may facilitate prior insurance authorizations, manage patient toxicities, counsel patients on side effects and adherence, and optimize dosing schedules and treatment regimens.3 For example, in a study on oral endocrine therapy for first-line treatment of patients with MBC, a quality improvement project was implemented and enrolled 53 patients.3 The study objective was to decrease the average treatment-day delays during the first 6 cycles of therapy.3 Pharmacists in the study had 640 interventions with patients, which included clinical recommendations and medication reconciliations.3 Decreased treatment-day delays were associated with incorporating pharmacists in clinic visits during the first 6 cycles of treatment along with providing meaningful interventions.3 A recent roundtable discussion elicited further information on how pharmacists can make a positive impact on the treatment of patients with HER2-positive or HER2-low MBC.

Shared decision-making with patients is essential, as well as meeting the patient where they are with education about their cancer. Many patients with HER2-positive MBC think traditional chemotherapy is the only option; however, with new targeted therapies and ADCs, the science behind these therapies will need to be explained so that patients understand side effects, overall survival, and progression-free survival to help them make informed decisions. Pharmacists counseling patients with MBC will want to determine how engaged the patient wants to be in their journey. What are their baseline expectations for treatment? Does the patient want to understand side effects and dose reductions at the start, and what medication options they have when they begin their treatment journey? What is their lifestyle and how does the treatment fit into it? Ensuring the patient’s goals and values are included in the treatment plans will set up the patient for successful outcomes.

Shared decision-making may also improve patients’ ability to remain adherent to treatment. Conver-sations can help patients understand treatment differences, the duration of treatment, and toxicities or side effects that are likely to occur with treatment. Just as important as understanding side effects ahead of time, inform patients how these will be managed with either pre-medication or dose reduction. Dose reduction can be very concerning for patients. However, if pharmacists communicate the clinical trial data in a patient-friendly manner, which demonstrates that dose reduction for some patients still leads to good progression-free survival, it can alleviate anxiety. Patients may also be curious to know if the clinical trial population was similar to them.

When discussing ADC therapy with patients, pharmacists should encourage questions. Terminology can be explained, such as what ADC therapy is and how it relates to HER2-positive or HER2-low breast cancer. Targeted therapy and cytotoxicity payload can also be explained to the patient. Since ADC therapy is unique with its synergistic mechanism, this is another issue to explain to the patient. Side effects of ADC therapy will need to be discussed along with how soon they occur and how to prepare for them to maintain quality of life and treatment adherence. Patients should be informed on how their treatment is administered and how often.

All this new information can be overwhelming for patients to digest. Reiterating key takeaways from provider appointments is one way pharmacists can help patients make informed decisions. Orienting patients to the process from appointments, treatments, potential lifestyle changes, and starting to plan their immediate future will empower them. Educating patients that not all breast cancer is the same by explaining classifications and using National Comprehensive Cancer Network guidelines to explain treatment recommendations is important to help patients feel more confident in treatment plans. Using internal resources and patient calendars that patients can take home and refer to will also provide clarity. Motivational interviews with patients should help to elicit their life goals while undergoing therapy for MBC. Understanding patient expectations and life goals is another avenue that can lead to treatment discussions with patients. Some common goals patients have is to extend their life, have a good quality of life, and to lead a productive life while engaging in regular activities. As ADC therapies are reviewed with the patient, the pharmacist will want to point out the unique potential side effects. For example, patients who enjoy time outdoors would need to be aware of any potential for photosensitivity associated with some medications. When patients can continue to lead a fulfilled lifestyle with slight modification during treatment, they will continue to be motivated to stay on treatment.

ADC therapy can improve the overall survival of patients with MBC.4,5 With both HER2-positive4,5 and HER2-low MBC,4 it provides good durability of response, deeper responses in some patients, and improved progression-free survival as well as reducing overall systemic chemotherapy side effects.4,5 ADC works in a synergistic manner and delivers cytotoxic chemotherapy in HER2-positive or HER2-low MBC. This may need to be explained to patients when they are considering treatment options. Discussions about consensus guidelines regarding when the various treatment options will be introduced in their cancer journey should be anticipated as well as discussions concerning biomarker status.

Clinical trial data can be presented to the patient, and where they fit into the data can help to inform decision-making. Clinical trial evidence is important to review to ensure that the best therapy is provided for the patient depending on their line of treatment. This can help patients feel comfortable with the decision process. Pharmacists can also introduce their real-world experience, particularly with dose reduction and anticipating and monitoring side effects. Inquiring about past treatments, if any, and treatment toxicities can help lead the discussion about ADCs. Neutropenia, nausea, vomiting, fatigue, and alopecia are side effects of ADC therapy, whereas interstitial lung disease/pneumonitis can be life-threatening.4,5 Anticipating and preparing for these side effects by having medications available at home or building in daily rest breaks to help with fatigue can help to minimize serious toxic effects, dose reductions, and therapy abandonment.

The patient should be provided with resources such as instructions to call with side-effect questions, internally developed materials, drug manufacturer reference materials, a treatment calendar that includes when side effects are likely to occur, and handouts from advocacy groups such as the Susan G. Komen Breast Cancer Foundation or Living Beyond Breast Cancer. Leveraging telepharmacy and patient portals can help pharmacists reach out and interact with patients on adverse events, and when and if they need to be seen by providers to manage side effects. These interactions with patients should also be conveyed by pharmacists with the patient’s treatment team.

Pharmacists play an important role in the successful treatment journey of patients with MBC. With the development of ADC therapy to treat HER2-positive and HER2-low MBC, monitoring clinical trial data and the drug development pipeline is important for pharmacists. With HER2-low MBC, ADC therapy gives patients options they previously did not have, while giving patients with HER2-positive or HER2-low MBC long progression-free survival times. By providing patient education, collaborating with the healthcare team, and listening, pharmacists can help patients with MBC become a little more informed about their treatment journey.


  1. Antonarelli G, Corti C, Tarantino P, et al. Management of patients with HER2-positive metastatic breast cancer after trastuzumab deruxtecan failure. ESMO Open. 2023;8:101608.
  2. Zhang H, Peng Y. Current biological, pathological and clinical landscape of HER2-low breast cancer. Cancers (Basel). 2022;15:126.
  3. Patel JV, Hughes DM, Ko NY. OPTIMAL Breast cancer care: effect of an outpatient pharmacy team to improve management and adherence to oral cancer treatment. JCO Oncol Pract. 2023;19:e306-e314.
  4. Enhertu [package insert]. Basking Ridge, NJ: Daiichi Sankyo, Inc. Published August 2022. Accessed November 7, 2023.
  5. Kadcyla [package insert]. San Francisco, CA: Genentech, Inc. Published 2022. Accessed November 7, 2023.
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