In the early work of the Nissen-Meier group from the Oslo Cancer Institute, it was shown that the appointment of cyclophosphamide immediately after surgery increases 10-year patient survival. The unpredictable nature of breast cancer and the need for long-term observation of patients make it very difficult to interpret recent results.
Nevertheless, it is obvious that adjuvant chemotherapy has made a significant contribution to increasing the effectiveness of treatment in terms of overall and disease-free survival of patients with tumors in the premenopausal lymph nodes. This particularly applies to the age group of 30-40 years. However, this conclusion was again made on the basis of data from the Early Breast Cancer Trialists Collaborating Group. As Pitot points out, a small increase in survival rate turns into thousands of lives saved, because breast cancer is a very common disease.
Adjuvant chemotherapy has also proven effective in treating patients without signs of lymph node involvement, but with large or aggressive primary tumors. From a prognostic point of view, poorly differentiated and fast-growing tumors, as well as tumors that are larger than 3 cm, are also unfavorable. Lack of hormonal receptors, nuclear polymorphism and expression of the erb-B2 protein are also among the poor prognostic signs.
Adjuvant chemotherapy should be prescribed to young patients under 35 years old with a diagnosis of cancer, regardless of the degree of involvement of the lymph nodes in the pathological process, since in this case the benefits of it are obvious. Recently, a “neoadjuvant” treatment regimen was tested on several randomized and controlled groups of patients with breast cancer. According to this scheme, the primary treatment is chemotherapy, not surgical methods or radiation therapy.
Although this concept of treatment of breast cancer seems interesting, it is still premature to talk about its effectiveness compared with conventional methods. This requires long-term observation of patients. However, it became obvious that in the treatment of patients with small operable tumors, preference should be given to adjuvant chemotherapy rather than radiotherapy.
This means that for the vast majority of patients with premenopausal tumors, including cases with lymph node lesions, the following sequence of treatment methods should be chosen: local resection of the mammary gland and removal of axillary lymph nodes, combined chemotherapy, and finally radiation therapy. Thus, the treatment strategy has changed a lot even compared to the one that was 10 years ago. If the patient had an ER-positive tumor, they should be given tamoxifen.
A separate article discusses in more detail the difficulties encountered in evaluating the effectiveness of early results of adjuvant therapy. These difficulties are especially acute in breast cancer, since a long period of observation of patients is necessary.
Therefore, it is not easy to answer the question whether adjuvant chemotherapy will be effective for all patients with early breast cancer. Probably, the advantages of this method are manifested among subgroups of patients, and its effectiveness cannot be significantly higher than the effectiveness of adjuvant hormone therapy drugs, which are usually much less toxic.
When combined therapy has a significant toxic effect, although it is not observed in all patients. This illustrates the case when it is necessary to compare a possible positive result of treatment with the patient’s quality of life. Obviously, prescribing a course of hormone therapy in patients with ER-positive premenopausal tumors is probably just as important for them as prescribing a course of chemotherapy.
Currently, adjuvant chemotherapy is widely used to treat patients with premenopausal tumors and, less commonly, in cases of postmenopausal tumors. It is almost always assigned to patients with a premenopausal tumor process, which is accompanied by damage to the lymph nodes, as well as in many cases of a common tumor that does not affect the lymph nodes. The CMF formulation (cyclophosphamide, methotrexate, 5-fluorouracil), which was used earlier, gave way to anthracycline-based formulations, such as AC (doxorubicin, cyclophosphamide) or FEC (using less toxic epirubicin).
After the publication of the NEAT research results, it became widely practiced to administer multiple courses of treatment with anthracyclines and CMF. However, for patients with a poor prognosis of the disease, taxan-based formulations are increasingly used. Four large randomized trials of paclitaxel and docetaxel (CALGB244) are currently published. One group of patients with lymphatic lesions was prescribed four courses of AS therapy, and another group, along with AS, received four courses of paclitaxel therapy. In the second group, significantly fewer relapses of the disease were observed, which manifested themselves already in the early periods of observation (after 21 months with 5-year follow-up).
This effect was disproportionately manifested in patients with tumors insensitive to hormones. Over the past few years, breast cancer treatment with the prescription of drugs in a mode of reducing the interval between successive doses has become increasingly used. The most significant example of such a “promotion” of chemotherapy is the work of Citron with employees, which shows a statistically significant increase in the survival rate of patients when treating them in a tight-dose mode.