Implications of body mass index on the biological and clinical effects of endocrine therapy and abemaciclib in the neoadjuvant setting

Lead Investigator: Maria Alice Franzoi, Jules Bordet Institute
Title of Proposal Research: Implications of body mass index on the biological and clinical effects of endocrine therapy and abemaciclib in the neoadjuvant setting
Vivli Data Request: 6494
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Obesity is a risk factor for the development of hormone receptor-positive breast cancer (e.g. Breast cells that contain special proteins called hormone receptors). These receptors ‘receive’ messages from hormones in the body and respond by telling the cells what to do. Cancer cells grow in response to the hormones estrogen or progesterone binding to the cells.)

In addition, overweight and obesity are factors associated with a worse prognosis when a patient is diagnosed with breast cancer. As obesity is a global public health problem that is increasing worldwide it is extremely important to understand whether the treatments available to treat breast cancer work differently in the context of overweight and obesity and what are the mechanisms in which the body mass index can interfere with the response to available treatments.

Recently, in a research conducted by our group, we observed that, for patients with hormone receptor-positive metastatic breast cancer, abemaciclib (a type of targeted treatment used for the treatment of breast cancer which inhibits the cell cycle regulators cyclin 4 and 6) plus endocrine as first or second-line therapy is superior to endocrine therapy alone regardless of body mass index.

Interestingly, we demonstrated that overweight and obese patients presented inferior response rates (percentage of patients whose cancer shrinks or disappears after treatment) and inferior rates of neutropenia (a blood condition characterized by low levels of neutrophils, which are white blood cells that protect our body from infections) when treated with abemaciclib plus endocrine therapy.

It has already been shown that metastatic samples differ from primary breast cancer in several aspects, such as the amount of immune cells that have moved from the blood into the tumor (tumor infiltrating lymphocytes), acquired mutations, and activated signaling pathways (which refers to a series of chemical reactions in which a group of molecules in a cell work together to control a cell function, in this case the division and multiplication of breast cancer cells).

Thus, it is important to investigate the impact of body mass index also in patients with early breast cancer.

Our objective is to use the data available from the NEOMONARCH study to compare the biological and clinical effects of endocrine therapy with or without abemaciclib given before surgery in overweight and obese patients vs. patients with normal weight. More precisely, we will compare the reduction of tumor proliferation rates, reduction of tumor size, and activation of the immune response towards the cancer cells after treatment according to the body mass index.

This research project can generate hypotheses for future studies that may improve the curative treatment of hormone receptor-positive breast cancer in overweight and obese patients.

Statistical Analysis Plan:

The present analysis aims to determine the prognostic impact of baseline body mass index in the biological and clinical effects of neoadjuvant treatment with anastrozole, anastrozole + abemaciclib, and abemaciclib alone. Study endpoints will be: mean changes in Ki67%, achievement of complete cell cycle arrest as per study definition, clinical and radiological response rates.

Continuous variables will be assessed using t-test, Mann-Whitney or Kruskall-Wallis test; categorical variables will be compared using chi-square or Fisher Exact test. The primary endpoint of the percent change in Ki67 expression from baseline to 2 weeks of treatment will be evaluated on the log Ki67 ratio scale. The analysis will be done using a linear model adjusting for the characteristics that will be different between the two body mass index groups (< 25 and ≥ 25). The least square mean estimates obtained from the model will be back-transformed to the percentage change scale. All statistical tests will be two-sided and no missing data will be imputed. We will consider a P-value <0.05 as statistically significant.

Requested Studies:

neoMONARCH: A Phase 2 Neoadjuvant Trial Comparing the Biological Effects of 2 Weeks of Abemaciclib (LY2835219) in Combination With Anastrozole to Those of Abemaciclib Monotherapy and Anastrozole Monotherapy and Evaluating the Clinical Activity and Safety of a Subsequent 14 Weeks of Therapy With Abemaciclib in Combination With Anastrozole in Postmenopausal Women With Hormone Receptor Positive, HER2 Negative Breast Cancer
Sponsor: Eli Lilly
Study ID: NCT02441946
Sponsor ID: 15805

Public Disclosures:

  1. Franzoi MA, Lambertini M, Ceppi M, Bruzzone M, de Azambuja E. Implication of body mass index (BMI) on the biological and clinical effects of endocrine therapy plus abemaciclib as neoadjuvant therapy for early breast cancer patients. Breast Cancer Res Treat. 2022 Jan 25. doi: 10.1007/s10549-022-06525-3.
  2. Maria Alice Franzoi, Matteo Lambertini, Marcello Ceppi, Marco Bruzonne, Evandro de Azambuja. Abstract P5-13-07: Implications of body mass index (BMI) on the biological and clinical effects of endocrine therapy and abemaciclib in the neoadjuvant setting. Cancer Res, 15 February 2022; 82 (4_Supplement): P5–13–07. doi: 10.1158/1538-7445.SABCS21-P5-13-07