Guest Editor’s Note: Chemotherapy and its side effects can lead to decreased physical activity and poor diet quality, resulting in unfavorable changes in physical functioning and quality of life. However, adopting healthy behaviors during cancer treatments can be challenging because of physical, emotional, and psychosocial barriers. In this article, Drs. Sanft and Irwin summarize findings from their study describing the impact of a 1-year lifestyle intervention, starting at chemotherapy initiation, on behavior changes in patients with breast cancer.

Tara Sanft, MD

Melinda L. Irwin, PhD, MPH

In observational studies, 25% to 55% of women with breast cancer do not complete chemotherapy as initially prescribed.¹ Relative dose intensity is an integrated measure of chemotherapy dose delays and reductions and is used to characterize chemotherapy completion.² A lower relative dose intensity (< 85%) has been shown to be a cutpoint whereby chemotherapy effectiveness and prognosis significantly worsen.³ Low relative dose intensity (< 85%), primarily because of treatment side effects, has been observed in 26% to 32% of women with breast cancer who receive adjuvant chemotherapy regimens.¹

Lifestyle Behaviors and Cancer Treatment

Higher levels of physical activity and better diet quality have been associated with lower breast cancer mortality in observational studies.^4,5 At diagnosis, many patients have low physical activity levels and suboptimal diets,⁶ and treatment often worsens these lifestyle behaviors.⁷

Physical activity and optimal nutrition may improve treatment adherence and efficacy. Recent ASCO guidelines recommend exercise during active treatment, based on evidence that exercise maintains or improves cardiorespiratory fitness, strength, fatigue, and other patient-reported outcomes.⁸ Exercise improved chemotherapy completion rates in women with breast cancer in two trials,^9,10 although trials in other cancer populations did not show a significant impact.¹¹ Of note, treatment adherence was a secondary outcome in all these studies.

LEANer Trial Details

If exercise and a high-quality diet improve chemotherapy completion rates, they could improve breast cancer prognosis. Pathologic complete response, defined as the disappearance of all invasive cancer in the breast after completion of neoadjuvant chemotherapy, is an important prognostic measure.¹² We examined the effect of a nutrition and exercise intervention vs usual care on relative dose intensity in women newly diagnosed with breast cancer initiating chemotherapy. A secondary endpoint was pathologic complete response in those receiving neoadjuvant chemotherapy.

Eligible participants were women being treated at Smilow Cancer Hospital Network at Yale–New Haven Hospital and the Dana-Farber Cancer Institute for newly diagnosed stage I to III breast cancer with chemotherapy (adjuvant or neoadjuvant). Inclusion criteria were willingness to participate in the study, ability to walk, and not currently meeting healthy lifestyle guidelines (< 150 min/wk of moderate- to vigorous-intensity physical activity, eating fewer than seven servings of fruits or vegetables daily), accessibility by telephone, and ability to understand instructions in English.

Participants were randomly assigned in a 1:1 fashion to a healthy diet and exercise intervention called lifestyle exercise and nutrition (LEAN) or usual care, which included referrals to supportive services at the discretion of the treating team. The intervention was delivered via a combination of in-person, telephone, or video per participant preference, study site location, and COVID-19 restrictions. The 16-session, year-long intervention included 4 weekly sessions in the first month, 2 biweekly sessions for months 2 and 3, and monthly sessions thereafter. The number of intervention sessions delivered during chemotherapy varied based on the duration of chemotherapy.

The intervention goal was for participants to adopt and practice a set of dietary and physical activity guidelines adapted from cancer survivorship guidelines.^13-15 The Healthy Eating Index–2015 was used as a measure of diet quality.¹⁶ Adherence to the physical activity guidelines was defined as 150+ min/wk of moderate- to vigorous-intensity physical activity or 75 min/wk of vigorous-intensity physical activity and twice-weekly resistance training.¹³

Data were extracted from the electronic medical record to calculate relative dose intensity. Pathologic outcomes were determined via the surgical pathology report. Pathologic complete response was defined as no residual invasive cancer in the specimen (ypT0N0 or ypTisN0).

Between February 2018 and July 2021, 173 women were enrolled and randomly assigned to the intervention (n = 87) or usual care (n = 86). Baseline characteristics were similar between groups. Women were 53 ± 11 years, with a mean body mass index of 29.7 ± 6.7 kg/m²; 71% were non-Hispanic White, 14% were Black, and 8% were Hispanic; the majority were college educated. Women were diagnosed primarily with stage I breast cancer (51%), with 42% receiving neoadjuvant chemotherapy and 58% receiving adjuvant chemotherapy.

Guest Editor

Jun J. Mao, MD, MSCE

Dr. Mao is the Laurance S. Rockefeller Chair in Integrative Medicine and Chief of Integrative Medicine Service at Memorial Sloan Kettering Cancer Center, New York.

Key Results

At the end of chemotherapy, women randomly assigned to the intervention reported significant increases in physical activity (143.4 ± 119.5 min/wk) compared with women randomly assigned to usual care (47.7 ± 99.6 min/wk, P < .001). More women randomly assigned to the intervention reported doing strength training during chemotherapy compared with those assigned to usual care (70% vs 7%, P < .0001). In addition, women randomly assigned to the intervention increased fruit and vegetable and dietary fiber intake during chemotherapy, whereas women assigned to usual care had adverse dietary changes (P < .01).

Overall adherence to chemotherapy was high in both groups, with a relative dose intensity of 92.9 ± 12.1% and 93.6 ± 11.1% of prescribed chemotherapy received for the intervention and usual care, respectively (P = .69). There was no difference in the proportion of patients in the intervention vs control groups who achieved at least 85% relative dose intensity (81% with the intervention vs 85% in controls, P = .44). Slightly more than one-third of women had a chemotherapy dose reduction and/or dose delay (38% with the intervention vs 36% with usual care, P = .80). The most common reasons for dose reductions and/or delays were neuropathy, infections, and hematologic toxicities.

Among the 72 women who received neoadjuvant chemotherapy, women randomly assigned to the intervention arm were more likely to have a pathologic complete response (53% vs 28% in the women receiving usual care, P = .037). Findings were limited to women with hormone receptor–positive/HER2-negative or triple-negative breast cancer subtypes.

Closing Thoughts

A healthy diet and exercise intervention delivered during chemotherapy significantly improved adherence to diet and exercise guideline recommendations compared with usual care. Although the intervention did not impact relative dose intensity, it was associated with a significantly higher pathologic complete response in patients with hormone receptor–positive/HER2-negative or triple-negative breast cancer undergoing neoadjuvant chemotherapy. Future studies are needed to validate these findings.

Dr. Sanft is Associate Professor of Medicine (Medical Oncology); Chief Patient Experience Officer; Medical Director, Survivorship Clinic; and Director, Communication Skills Course, Yale School of Medicine, New Haven, Connecticut. Dr. Irwin is Associate Dean of Research and Susan Dwight Bliss Professor of Epidemiology (Chronic Diseases); Deputy Director (Public Health), Yale Center for Clinical Investigation; and Deputy Director, Yale Cancer Center, New Haven, Connecticut.

DISCLOSURE: Dr. Sanft and Dr. Irwin reported no conflicts of interest.

REFERENCES

1. Weycker D, Barron R, Edelsberg J, et al: Incidence of reduced chemotherapy relative dose intensity among women with early stage breast cancer in US clinical practice. Breast Cancer Res Treat 133:301-310, 2012.
2. Longo DL, Duffey PL, DeVita Jr VT, et al: The calculation of actual or received dose intensity: A comparison of published methods. J Clin Oncol 9:2042-2051, 1991.
3. Bonadonna G, Valagussa P, Moliterni A, et al: Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: The results of 20 years of follow-up. N Engl J Med 332:901-906, 1995.
4. Neilson HK, Farris MS, Stone CR, et al: Moderate-vigorous recreational physical activity and breast cancer risk, stratified by menopause status: A systematic review and meta-analysis. Menopause 24:322-344, 2017.
5. Schmid D, Leitzmann MF: Association between physical activity and mortality among breast cancer and colorectal cancer survivors: A systematic review and meta-analysis. Ann Oncol 25:1293-1311, 2014.
6. Arem H, Mama SK, Duan X, et al: Prevalence of healthy behaviors among cancer survivors in the United States: How far have we come? Cancer Epidemiol Biomarkers Prev 29:1179-1187, 2020.
7. Irwin ML, Crumley D, McTiernan A, et al: Physical activity levels before and after a diagnosis of breast carcinoma: The Health, Eating, Activity and Lifestyle (HEAL) study. Cancer 97:1746-1757, 2003.
8. Ligibel JA, Bohlke K, May AM, et al: Exercise, diet, and weight management during cancer treatment: ASCO guideline. J Clin Oncol 40:2491-2507, 2022.
9. Courneya KS, Segal RJ, Mackey JR, et al: Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: A multicenter randomized controlled trial. J Clin Oncol 25:4396-4404, 2007.
10. van Waart H, Stuiver MM, van Harten WH, et al: Effect of low-intensity physical activity and moderate- to high-intensity physical exercise during adjuvant chemotherapy on physical fitness, fatigue, and chemotherapy completion rates: Results of the PACES randomized clinical trial. J Clin Oncol 33:1918-1927, 2015.
11. Bland KA, Zadravec K, Landry T, et al: Impact of exercise on chemotherapy completion rate: A systematic review of the evidence and recommendations for future exercise oncology research. Crit Rev Oncol Hematol 136:79-85, 2019.
12. von Minckwitz G, Untch M, Blohmer JU, et al: Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30:1796-1804, 2012.
13. Campbell KL, Winters-Stone KM, Wiskemann J, et al: Exercise guidelines for cancer survivors: Consensus statement from international multidisciplinary roundtable. Med Sci Sports Exerc 51:2375-2390, 2019.
14. Rock CL, Thomson CA, Sullivan KR, et al: American Cancer Society nutrition and physical activity guideline for cancer survivors. CA Cancer J Clin 72:230-262, 2022.
15. Hastert TA, Beresford SAA, Patterson RE, et al: Adherence to WCRF/AICR cancer prevention recommendations and risk of postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 22:1498-1508, 2013.
16. Anderson C, Harrigan M, George SM, et al: Changes in diet quality in a randomized weight loss trial in breast cancer survivors: The Lifestyle, Exercise and Nutrition (LEAN) study. NPJ Breast Cancer 2:16026, 2016.