**1. Introduction**

7

Approximately 80% of breast cancer patients have hormone-receptor-positive tumors. In these patients, adjuvant endocrine therapy (AET) is widely used, which includes tamoxifen or aromatase inhibitors (AIs) with or without GnRH agonists, depending on tumor characteristics and menopausal state. In post-menopausal women, AIs represent the main adjuvant endocrine treatment, as they have demonstrated superior clinical outcomes compared to tamoxifen, while in premenopausal patients, different options are available, such as tamoxifen alone or tamoxifen plus GnRH agonists, with a switch to AIs alone when menopause occurs [1,2]. In particular, in young women with high-risk disease, the addition of GnRH agonists to the aromatase inhibitor exemestane significantly improves DFS and reduces the recurrence rate, as shown by SOFT and TEXT trials [3,4]. International guidelines agree with a standard treatment duration of 5 years, but a 10-year extended therapy may be suggested depending on tumor and patient individual characteristics with the support of specific algorithms such as CTS5 [5]. It has been demonstrated that AET reduces the risk of recurrence by 30% and mortality by 40% in patients with hormone-receptor-positive breast cancer and that extended therapy determines a further reduction, as shown by aTTom and ATLAStrials,aswellasMA17R,DATA,IDEALandNSABPB42trials[6–14].

Despite these benefits, AET is burdened by considerable side effects and poor adherence to treatment, which represents a significant problem. Regarding side effects, the anti-estrogenic action of tamoxifen causes hot flashes, vaginal dryness, sexual dysfunction and dyspareunia,

**Citation:** Rosso, R.; D'Alonzo, M.; Bounous, V.E.; Actis, S.; Cipullo, I.; Salerno, E.; Biglia, N. Adherence to Adjuvant Endocrine Therapy in Breast Cancer Patients. *Curr. Oncol.* **2023**, *30*, 1461–1472. https://doi.org/ 10.3390/curroncol30020112

Received: 27 November 2022 Revised: 7 January 2023 Accepted: 18 January 2023 Published: 21 January 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

while its pro-estrogenic effect on endometrium increases the risk of endometrial hyperplasia, polyps and, rarely, endometrial cancer; moreover, it increases the risk of deep venous thrombosis and pulmonary thromboembolism. On the other side, AIs mostly determine arthralgia, joint pain and osteoporosis, as well as weight gain, headache, insomnia, mood changes and hypercholesterolemia [15,16]. Many clinical trials and epidemiological studies show that side effects have a significant impact on the quality of life and play a primary role in the suboptimal adherence to AET in breast cancer patients [17–20]. The discontinuation rate reported in the literature in the first 5 years of treatment is about 50% with a progressive decrease in adherence from the first year (87%) to the third (79%) and fifth (50%) [3,21–24].

It has been demonstrated that the early discontinuation of AET is related to a decline in survival, increased recurrence risk and reduced DFS, as well as increased medical costs and low quality of life due to disease progression and treatment [25–27].

Another significant element associated with non-adherence to AET is poor patient– physician communication, an inadequate explanation of the type and severity of side effects at the beginning of treatment and poor consideration of them during follow-up visits [28–31]. In fact, many studies highlighted the importance of discussing potential concerns and establishing a trustful patient–physician relationship in the acceptance of AET and adherence to treatment [32–35].

The aim of this study is to analyze the type, incidence and severity of AET side effects and determine their impact on adherence to treatment. We also intend to evaluate the importance of patient–physician communication and the benefit of medical and psychological support strategies.

#### **2. Materials and Methods**

In this retrospective observational study, we analyzed a population of 373 patients with hormone-receptor-positive breast cancer currently or previously treated with AET (tamoxifen, AI, GnRH agonists). A specific questionnaire was administered to these patients during one of their follow-up visits at the Breast Unit of "Mauriziano Umberto I" Hospital in Turin from January 2021 to December 2021.

The questionnaire was composed of 31 questions and 5 sections: AET tolerance and side effects; adherence to treatment (regularity of assumption, change or suspension of treatment due to intolerance); adherence and tolerance to extended therapy; patient–physician communication and strategies suggested to control side effects; and the importance and efficacy of medical and psychological support (Appendix A).

The study included patients with hormone-receptor-positive breast cancer (luminal A and luminal B) who underwent any type of surgery (mastectomy or conservative surgery) followed by AET (tamoxifen, AI, GnRH agonists) from at least 6 months, also including those in the extended therapy regimen. We did not include in our analysis patients on exclusive endocrine therapy and patients with breast cancer recurrence, nor did we include patients who used both tamoxifen and aromatase inhibitors because it could represent a confounding factor. We did not set any limit in terms of time from diagnosis or from the beginning of follow-up.
