Hormonal Therapy in Oncology

Impact of exogenous hormones and screening rules

The use of menopausal hormone therapy (MHT) and oral contraceptives involves the introduction of exogenous estrogens into the body. In oncology, these substances are considered a significant risk factor for the development of breast cancer (BC). This is why a thorough examination is required before starting any hormonal treatment.

Baseline screening includes visual inspection and palpation. The choice of instrumental method depends on the patient's age:

• Under 40 years of age, ultrasound (US) is the primary method.
• At 40 years and older, mammography performed strictly in two projections serves as the gold standard.

Results are evaluated using the BI-RADS system, and tissue density is classified on the ACR scale. If a woman is found to have high radiologic density (types C or D), the sensitivity of mammography drops critically—down to 48%. In such situations, the protocol requires mandatory additional ultrasound. Consultation with an oncomammologist before starting MHT is strictly indicated if node formations are detected, for any BI-RADS category other than 1 and 2, high tissue density, and the presence of other significant risk factors.

Side effects of systemic treatment

Antineoplastic therapy is accompanied by a number of specific adverse events. Hormonal treatment has a clear toxicity profile depending on the drug group:

1. Antiestrogens (e.g., tamoxifen) frequently provoke vasomotor symptoms (hot flashes). In addition, they significantly increase the risk of thromboembolic complications and can cause endometrial hyperplasia.
2. Aromatase inhibitors lack these drawbacks, but their intake is associated with bone mass loss (development of osteoporosis) and pronounced joint pain (arthralgia).

For comparison, classical chemotherapy more frequently causes myelosuppression, alopecia, mucositis, nausea and vomiting, as well as peripheral neuropathy. The use of anthracyclines and targeted anti-HER2 therapy is associated with a high risk of cardiotoxicity. Radiation therapy can be complicated by radiation dermatitis, tissue fibrosis, and upper extremity lymphedema (when irradiating regional lymphatic drainage pathways).

Hereditary cancer syndromes

Hormone-dependent tumors are often associated with genetic abnormalities. Mutations in the BRCA1 and BRCA2 genes form a single hereditary syndrome linking breast cancer and ovarian cancer.

In malignant ovarian neoplasms (especially high-grade serous and endometrioid carcinomas), BRCA mutations occur in approximately 15% of cases. Identifying this genetic defect is of immense clinical significance: it indicates high sensitivity of tumor cells to alkylating agents, platinum drugs, and PARP inhibitors.

In addition, this syndrome also affects the pancreas. About 10% of cases of cancer at this site have a hereditary nature. The presence of BRCA1, BRCA2, or PALB2 mutations directly determines the management tactics for such patients—it is preferable to prescribe platinum-based chemotherapy regimens to them.

Differential diagnosis and therapy limitations

When suspected of breast cancer, it is important to rule out benign yet clinically similar pathologies that may be detected during screening:

• Breast sarcoidosis. Manifests as a dense, painless formation on palpation. The diagnosis is confirmed by biopsy, which reveals multiple non-caseating granulomas. At the same time, it is critically important to differentiate the condition from tuberculosis.
• Idiopathic granulomatous mastitis. On mammograms, it mimics a malignant process: focal asymmetry, skin thickening, and enlargement of axillary lymph nodes are visualized.

The prescription of systemic therapy has a number of generally accepted contraindications. These include pregnancy (limiting the use of most cytostatics and radiation therapy), deep myelosuppression, decompensated comorbidities, and severe organ failure. Assessment of heart, liver, and kidney function is especially important before prescribing cardiotoxic drugs.

Class and exam questions

What else to study on this topic

• Criteria for evaluating formations using the BI-RADS system
• Classification of breast radiologic density according to ACR
• Mechanisms of cardiotoxicity of anthracyclines and targeted anti-HER2 therapy
• Specifics of using PARP inhibitors in BRCA-associated tumors
• Treatment protocols for idiopathic granulomatous mastitis

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.