Breast cancer during pregnancy is a malignant neoplasia of the breast, detected during gestation, lactation or within 12 months after delivery. It is manifested by nodular or diffuse compaction of the mammary glands, their heaviness and soreness, discomfort, pain in the areola area, discharge from the nipple, local skin changes, an increase in axillary lymph nodes. It is diagnosed by ultrasound, trepanobiopsy, MRI of the mammary glands. During gestation, surgical methods of treatment are used (usually modified versions of radical mastectomy), chemotherapy according to the AC scheme. After childbirth, therapy is supplemented with hormonal drugs and radiation techniques.
C50 Malignant neoplasm of the breast
Breast cancer during pregnancy are the second most common type of neoplasia diagnosed in pregnant women. Their occurrence is 1:3,000 — 1:10,000 gestations. The average age of women diagnosed with breast cancer associated with pregnancy is 33 years. Up to 82% of patients detect the neoplasm independently in the first trimester, while in almost 3/4 of cases, late stages of neoplasia with tumor sizes from 6 to 15 cm are diagnosed, and every fifth pregnant woman has metastases in internal organs. Due to the untimely diagnosis of the disease, the delay in starting treatment is on average 2-3.5 months.
The etiology of breast cancer during pregnancy is the same as in non-pregnant women. In 5-10% of cases, the development of cancer is due to an inherited mutation of the BRCA1/BRCA2 genes. In the remaining patients, the neoplasm occurs against the background of dishormonal conditions, the effects of adverse environmental factors (mutagenic chemicals, radiation, etc.), insufficient immunity. As a rule, tumors detected in the mammary glands of pregnant women occur before conception, but their growth may accelerate against the background of physiological gestational changes. According to experts in the field of oncology and obstetrics, specific provoking factors of rapid oncogenesis during pregnancy are:
- Hormonal restructuring. In more than 70% of cases, breast cancer in pregnant women is estrogen-dependent (ER+). During gestation, the level of estrogen in the blood increases by almost 30 times. Under the influence of hormones, the mammary glands are prepared for lactation: the breast swells, the number of alveoli and milk ducts increases in it. Hyperestrogenic stimulation may contribute to the faster development of cancer cells.
- Decreased immunity. Since the fetus is genetically alien to the mother’s body, physiological changes in the immune system of pregnant women are aimed at reducing overall reactivity. Due to an increase in the number of T-suppressors, a decrease in the level of T-helpers, the appearance of blocking antibodies, the effector link of immunity is suppressed. As a result, the immune system is worse at detecting and destroying its own degenerating cells.
The probable mechanism of breast cancer development in pregnant women is based on the stimulation of the growth of transformed cells by estrogens and progesterone. The increased estrogenic effect induces the synthesis of growth factors, under the influence of which the epithelial cells of the mammary glands, including malignant tumors, proliferate. At the same time, cellular apoptosis is inhibited, due to the induced transcription of vascular endothelial growth factor, pathological neovascularization begins.
Since estrogens are able to neutralize the effect of inhibitory growth factors, negative feedback is activated, stimulating cellular hyperplasia. One of the estrogenic effects is a rapid increase in the number of micrometastases caused by stimulation of the so-called dormant metastatic formations. The role of progesterone in the oncogenesis of breast neoplasia is still being clarified. Its effects may be associated with the maintenance of cyclic proliferation of glandular cells during gestation and growth stimulation with a potential modification of the response of normal and degenerated glandular epithelium.
The systematization of breast cancer during pregnancy is based on the same criteria as outside the gestational period — the anatomical location of neoplasia, its size, features of metastasis to lymph nodes and distant organs, histological structure, the level of cellular differentiation, the type of malignized cell receptors expressed. The most significant role in the development of optimal tactics of pregnancy support is played by the classification of tumors by stages of development. Oncomammologists distinguish:
- Non-invasive cancer (carcinoma in situ). Neoplasia is localized in the milk duct or lobule. The lymph nodes are intact. There is no clinic. Cancer becomes an accidental finding during routine examination. The most favorable form. It is possible to continue gestation after surgical treatment.
- Stage I cancer. The maximum diameter of the neoplasm does not exceed 2 cm. Neoplasia grows into the surrounding breast tissue, but does not metastasize. It can be determined clinically in the form of a nodular seal. Performing surgical intervention allows you to preserve pregnancy.
- Stage II cancer. At stage IIA, the tumor has a size of up to 2 cm with metastasis to the axillary lymph nodes on the affected side or up to 5 cm without metastases. In stage IIB cancer, the size of neoplasia is 2-5 cm in the presence of lymph node metastases or from 5 cm or more in their absence. Radical mastectomy is indicated to preserve gestation.
- Stage III cancer. The tumor grows to 5 centimeters or more, or conglomerates of soldered axillary lymph nodes are noted, cancer germination into the skin of the breast, chest tissue, damage to subclavian and supraclavicular lymph nodes. Distant metastases are possible.
- Stage IV cancer. There is a massive lesion of the breast with the germination of surrounding tissues, dissemination into the skin, ulceration. It is possible to involve the second breast, axillary lymph nodes on the opposite side in the process. Multiple distant metastases are characteristic.
At the III-IV stages of the oncoprocess, at the request of the patient and her relatives, it is permissible to preserve gestation with early delivery within the time of sufficient viability of the child. In such cases, performing a radical surgical intervention allows you to stop the spread of the tumor and begin active therapy in the postpartum period. The appointment of some chemotherapy drugs is possible from the 15th week of gestation.
Symptoms of breast cancer during pregnancy
Although gestational physiological changes in tissues complicate the detection of malignant volumetric formation, there are marker signs that increase cancer alertness. The development of cancer may be indicated by the appearance of a node or an unformed seal in one of the mammary glands, soreness and severity. In some patients, against the background of general swelling, the shape of the affected breast changes asymmetrically, irregularities, areas of retractions or local swelling appear on the skin.
There is often tingling, pain in the nipple-areolar region, the nipple may be retracted, there are sucrovichnye secretions. In the presence of regional metastases in the armpit, enlarged lymph nodes are detected on the affected side, in more severe cases, lymph nodes are probed above and under the clavicle, in the opposite axillary cavity. Signs of general intoxication in the form of loss of appetite, weight loss, increasing weakness and fatigue are characteristic only for the terminal stages of the disease.
Breast cancer during pregnancy that occurs in pregnant women can progress rapidly and be complicated by metastasis. Common forms of the disease are detected in 72-85% of patients, 20% of women have internal organs affected by metastases. In some cases, inflammation of the tissues surrounding the tumor develops. According to most obstetricians and gynecologists, breast cancer does not have a negative effect on the child, however, in the late stages of the disease, in the presence of tumor intoxication, fetal hypoxia is possible. The use of chemotherapeutic drugs in the II-III trimesters can provoke premature birth, myelosuppression in women and children, fetal development delay, stillbirth, massive postpartum bleeding, infectious complications (endometritis, chorioamnionitis, etc.).
Since pregnant women often regard the initial signs of a tumor as specific changes in the mammary glands before lactation, breast cancer during gestation is usually diagnosed at later stages. Diagnostically significant radiological methods of examination during pregnancy are used only to a limited extent due to the possible negative effect on the fetus, however, other modern techniques allow to identify the tumor and correctly assess the stage of the cancer process. The most informative when detecting malignant neoplasia of the breast are:
- Mammosonography. Ultrasound of the mammary glands is the optimal method of screening diagnosis of malignant tumors in pregnant and lactating women. The information content of ultrasonography, supplemented with color and energy Dopplerography, reaches 97%. Usually, on ultrasound, cancer looks like a hypervascularized hypoechoic formation of irregular shape and heterogeneous structure. With the help of ultrasound, it is convenient to examine regional lymph nodes.
- Trepanobiopsy of the breast. The material obtained with the help of a biopsy gun is used to determine the morphological structure of the neoplasm and its immunohistochemical profile (receptor status, amplification of the Her2-neu gene, proliferative index Ki-67, etc.). Trepanobiopsy is more informative than puncture biopsy, allows to verify the diagnosis in 99.0-99.8% of cases.
- Tomography. Mammary MRI is performed when receiving ambiguous sonography results. Layered visualization makes it possible to estimate the size and prevalence of neoplasia as accurately as possible. MRI of the whole body is recommended to detect metastases. In the first trimester, scanning is carried out with caution due to possible cavitation and overheating of the embryo. Contrasting is allowed in exceptional cases.
Mammography is rarely prescribed to pregnant women with suspected breast cancer, which is associated with a possible damaging effect on the fetus and obtaining false negative results in 25% of cases. As additional methods of examination, it is recommended to determine the cancer marker CA 15-3, cytology of a smear obtained from the nipple of the affected breast, risk assessment of BRCA-associated cancer, ductoscopy, radiothermometry of the breast, electroimpedance mammography. The disease is differentiated with mastitis, benign neoplasia (cysts, adenomas, fibroadenomas, lipomas, leaf-shaped tumors), galactocele, hamartomas, lymphomas, sarcomas, tuberculosis. In addition to the oncologist, the patient is advised by an oncologist, a chemotherapist, a surgeon, a phthisiologist, an infectious disease specialist.
Treatment of breast cancer during pregnancy
If earlier detection of a malignant neoplasm of the breast served as a sufficient reason for termination of pregnancy, in recent decades, strategies involving early initiation of therapy and preservation of gestation have been used. The choice of medical tactics in each specific case of cancer is carried out individually, taking into account the stage of the process, gestational age and the decision of the pregnant woman. In the 1st trimester, if invasive forms of the tumor are detected, it is recommended to terminate the pregnancy with a medical abortion, in the 2nd-3rd — if the patient wishes, extend it to the minimum possible term of birth of a viable fetus. After artificial termination of gestation, treatment is performed according to standard protocols of oncological care. When deciding to save a child, the following options can be used:
- Surgical treatment. The most justified intervention in the early stages of cancer is a radical mastectomy, supplemented, if necessary, by axillary dissection without subsequent radiation therapy. Lumpectomy, quadranectomy, and sectoral breast resection are performed less frequently. Oncoplastic operations are not recommended. The scope and duration of the intervention in the later stages of the disease are determined individually.
- Appointment of chemotherapy drugs. Antineoplastic agents can be used after 14 weeks of gestational age. The later the drug treatment is started, the less likely the fetus is to develop deformities. The drugs of choice are alkylating cytostatics and anthracycline antibiotics. In common forms of cancer, neoadjuvant polychemotherapy is used as a preparatory stage before radical surgery.
Hormone therapy, which is most effective in receptor-positive forms of cancer, is not carried out in pregnant women due to the teratogenic effect of estrogen antagonists. The appointment of radiation therapy is possible only after the end of gestation. The recommended method of delivery is natural childbirth. Cesarean section is performed only in the presence of obstetric indications or severe extragenital pathology incompatible with labor loads.
Prognosis and prevention
The survival rates of patients who were diagnosed with breast cancer during pregnancy do not differ from the data for groups of non-pregnant women. Termination of gestation does not affect the outcome of the disease. However, in general, the prognosis is more serious, since common forms of cancer are often detected in pregnant women. The minimum safe interval from the moment of completion of treatment to the next pregnancy, according to various authors, is from 6 months to 5 years. The main task of breast cancer prevention is the detection of tumors in the early stages using screening methods (ultrasound, mammography).