Prognostic role of clinical and biological factors and parameters of hormonal profile in patients with primary inoperable HER2-negative breast cancer

Relevance. Breast cancer (BC) is among the most common cancers and the leading causes of cancer death in women worldwide. Much attention is paid to the problem of its hormoneresistance; however, the issues of using prognostic markers and predictors in routine cancer clinical practice remain unresolved.

Aim. Study and analysis of prognostic significance of clinical and biological factors and parameters of the hormonal profile in patients with primary inoperable HER2-negative breast cancer receiving neoadjuvant chemotherapy.

Materials and methods. The study included 162 patients with locally advanced primary inoperable HER2-negative breast cancer. Patients were divided into 2 groups. Group 1 included 58 patients with early disease progression within 6 to 12 months after radical surgical treatment. Group 2 included 104 patients with no disease progression within 2 years after radical surgical treatment. In all cases, diagnosis was verified histologically and immunohistochemically. Levels of prolactine, progesterone, estradiol, luteinizing hormone (LH), follicle-stimulating hormone, testosterone and cortisol were measured by RIA. The blood plasma values in 20 healthy donors were used as reference one. The data were processed using the Statistica 7.0 and MedCalc (version 9.3.5.0) programs. All patients received combination antitumor treatment according to clinical guidance.

Results. An analysis of the overall (OS) and event-free (EFS) survival in group 1 showed that the median EFS in patients with luminal B BC was 9 months, with triple-negative BC (TNBC) – 8 months. 6-month EFS in luminal B subtype was 87.5%, in TNBC – 79.4%, p=0.37985. 1-year EFS was 1.72±1.7% regardless of the biological subtype. The median OS in luminal B BC was 25 months, in TNBC – 26 months. 1-year OS in luminal B BC – 100%, in TNBC – 93.9%, p=0.138. 2-year OS in luminal B BC – 54.2%, in TNBC – 55.9%, p=0.697. 3-year survival in luminal B BC – 37.5%, in TNBC – 41.2%, p=0.639. An analysis of OS and EFS in group 2 showed that the median EFS was not reached for all biological subtypes. 3-year survival in the group was 100% regardless of the biological subtype. The median OS was not reached for all biological subtypes. 3-year OS in the group was 100%. An analysis of the hormonal profile in the treatment dynamics showed decreased levels of estradiol in all groups of patients (by 1.6 times). In group 1, progesterone was decreased by 2.1 times, testosterone by 2.4 times and LH by 2.1 times in all BC subtypes (p≤0.05). Patients of group 2 showed 2 times reduced cortisol and 3 times reduced prolactin in all BC subtypes, while LH levels were elevated by 1.6 times in luminal A and B BC.

Conclusion. Aggressive course was observed similarly in triple-negative cancer as well as in luminal cancer with primary hormone resistance. Studying of pituitary and sex hormones and cortisol have a great clinical significance in patients with all biological subtypes of BC. This should be taken into account when predicting the course of the disease and developing further treatment options.