Commentary: Early Breast Cancer Treatment Strategies and Acupuncture, January 2023

Erin Roesch, MD

The risk for disease recurrence, and specifically distant relapse, for women with high-risk early breast cancer highlights the need for novel therapies in this population.^2,3 The phase 3 randomized monarchE trial investigated the role of the CDK4/6 inhibitor abemaciclib combined with endocrine therapy vs standard endocrine therapy alone in 5637 patients with high-risk (≥ 4 positive axillary nodes or 1-3 positive nodes and either grade 3 tumor, tumor size ≥ 5 cm or Ki-67 ≥ 20%) hormone receptor–positive/HER2-negative early breast cancer. At a median follow-up of 42 months, the median invasive disease-free survival (iDFS) benefit was sustained with abemaciclib + endocrine therapy vs endocrine therapy alone (HR 0.664; nominal P < .0001); the absolute 4-year iDFS benefit was 6.4% (85.8% in the abemaciclib + endocrine therapy group vs 79.4% in the endocrine therapy–alone group). Furthermore, this effect appeared to deepen over time, as the previous absolute iDFS differences were 2.8% (2 years) and 4.8% (3 years). Abemaciclib was associated with a higher rate of grade 3 or higher adverse events (49.9% vs 16.9%), the most common being neutropenia, leukopenia, and diarrhea (Johnston et al). Although adjuvant palbociclib trials (PALLAS⁴ and PENELOPE-B⁵) did not meet their primary endpoint, longer follow-up of monarchE and results from NATALEE with ribociclib are anxiously awaited to further define the role of CDK4/6 inhibitors in this space.

Aromatase inhibitors (AI) are an integral component of treatment for hormone receptor–positive breast cancer for many women. However, joint pain and stiffness associated with these agents can affect compliance. Various management strategies, including trials of alternative AI or endocrine therapies and pharmacologic (duloxetine) and non-pharmacologic (acupuncture,⁶ exercise) modalities, have been investigated. A randomized trial including 226 women with early-stage breast cancer receiving AI therapy with baseline joint pain (Brief Pain Inventory Worst Pain [BPI-WP] item score of ≥ 3) evaluated whether true acupuncture (TA) provided a sustained reduction in pain symptoms compared with sham acupuncture (SA) or waiting-list control (WC). Acupuncture protocols consisted of 6 weeks of intervention (2 sessions per week) followed by 1 session per week for another 6 weeks. At 52 weeks, mean BPI-WP scores were 1.08 points lower in the TA group compared with the SA group (P = .01) and were 0.99 points lower in the TA group compared with the WC group (P = .03) (Hershman et al). These data support consideration of acupuncture as a mechanism to help maintain patients on aromatase inhibitors, particularly for patients who wish to avoid or have not received benefit from pharmacologic therapy.

Additional References

1. Puglisi F, Gerratana L, Lambertini M, et al. Composite risk and benefit from adjuvant dose-dense chemotherapy in hormone receptor-positive breast cancer. NPJ Breast Cancer. 2021;7:82. Doi: 10.1038/s41523-021-00286-w
2. Salvo EM, Ramirez AO, Cueto J, et al. Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis. Breast. 2021;57:5-17. Doi: 10.1016/j.breast.2021.02.009
3. Sheffield KM, Peachey JR, Method M, et al. A real-world US study of recurrence risks using combined clinicopathological features in HR-positive, HER2-negative early breast cancer. Future Oncol.2022;18:2667-2682. Doi: 10.2217/fon-2022-0310
4. Mayer EL, Dueck AC, Martin M, et al. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): Interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2021;22(2):212-222. Doi: 10.1016/S1470-2045(20)30642-2
5. Loibl S, Marmé F, Martin M, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer-The Penelope-B trial. J Clin Oncol. 2021;39(14):1518-1530. Doi: 10.1200/JCO.20.03639
6. Liu X, Lu J, Wang G, et al. Acupuncture for arthralgia induced by aromatase inhibitors in patients with breast cancer: A systematic review and meta-analysis. Integr Cancer Ther. 2021;20:1534735420980811. Doi: 10.1177/1534735420980811