Breast cancer is the most common type of cancer in women in the Western world.
Mortality from the disease has decreased significantly in recent years, which is mainly attributed to the following two factors: a) the diagnosis of the disease at an earlier stage with the widespread application of screening and b) progress in the systematic treatment of cancer of breast.
Coping
Surgical treatment
The purpose of surgical treatment is to improve the therapeutic results and the best aesthetic result. The rule for choosing surgical treatment is the molecular classification of the neoplasm and the presence of BRCA1 and BRCA2 gene mutations.
The majority (about 72%) of breast cancers are hormone sensitive, (Luminal A, Luminal B), i.e. they express hormone receptors [HR]+/HER2-). The second most common subtype (at about 13%) is triple negative breast cancer (TNBC, or HR – /HER2-). Hormone-sensitive HER2-positive breast cancer (HR+/HER2+) (Luminal B), accounts for approximately 10% and hormone-negative HR-/HER2-positive breast cancer occurs in 5%.
Surgical removal of the tumor remains the primary treatment for the majority of women with breast cancer. In early breast cancer, surgical breast conservation has replaced mastectomy in many cases.
Breast conserving surgery involves removing the tumor or part of the breast and a small number of lymph nodes (sentinel lymph node or lymph nodes), resulting in the minimization of postoperative complications. In cases where breast conservation is impossible, preoperative systemic treatment results in avoiding mastectomy. In some cases, in which the aesthetic result is not satisfactory, tumor removal can be combined with restorative techniques to improve the aesthetic result (oncoplasty).
The majority of hormone-dependent neoplasms can be taken directly to surgery.
Induction therapy, as preoperative therapy is called, is used, mainly in locally advanced breast cancer, in large tumors with the aim of reducing the burden of the disease and the best surgical outcome. It can also be used in specific histological subtypes. It has been shown in clinical studies, that in these patients, with the systematic preoperative treatment, a complete remission and a better outcome of the disease is achieved in the majority of patients. These subtypes are HER 2 positive and triple negative breast cancer (TNBC). In recent years, the treatment of breast cancer has been completely individualized and this is due to the fact that we have gained a better knowledge of the molecular biology of the neoplasm.
Systemic therapy – new drugs
The postoperative treatment is determined by the results of the surgery and additionally by the results of specialized tests that give us the genetic signature of the tumor (Oncotype DX, Mammaprint, etc.).
New drugs
Hormone-dependent (HR) positive breast cancer.
Postoperative treatment of hormone-positive breast cancer includes hormone therapy, either as monotherapy or in combination with other targeted therapies.
For metastatic disease, combinations of hormone therapy with CDK4/6 cyclin-dependent kinase inhibitors, as well as mTOR inhibitors, are used. Studies show that the combinations are quite effective with a manageable toxicity profile. Some of the CDK4/6 inhibitors have received approval and are also given in early breast cancer.
Another target in hormone-positive metastatic breast cancer is the PIK3CA mutation for which there is a targeted drug, Alpelisib, which in clinical trials has shown that it can significantly benefit patients who carry the mutation.
HER2 positive breast cancer
In recent years the success of trastuzumab (Herceptin), pertuzumab (Perjeta) and Ado-trastuzumab emtastine (Kadcyla) in patients with HER2 positive (+++) breast cancer has sparked interest in the HER2 oncogene as a therapeutic target. New drugs, such as margetuximab (Margenza) as well as trastuzumab deruxtecan (Enhertu), which appear to be effective in selected patients, have been shown in clinical trials to be safe and effective when used in previously treated patients with metastatic HER2-positive breast cancer.
Recent studies show that using the latter drug (Enhertu) in patients with low Her2(low) load (1+) has great therapeutic effects in metastatic disease.
So do tyrosine kinase inhibitors (TKIs). Oral drugs, such as tucatinib (Tukysa), lapatinib (Tyverb), neratinib (Nerlynx), appear to benefit patients with brain metastases and play an important role in the treatment of metastatic HER2-positive breast cancer.
Triple negative breast cancer (TNBC)
Recently the interest in triple negative breast cancer has turned to combinations of classical chemotherapy with immunotherapy. Agents instead of PD-1/PD-L1 (Pembrolizumab, Atezolizumab) are being tested in clinical trials in metastatic as well as early breast cancer with encouraging results so far.
Finally, PARP inhibitors have been identified as therapeutic targets in patients carrying mutations, such as BRCA1/2 and PALB2, especially in the treatment of metastatic as well as early TNBC breast cancer.
She writes:
Irini Karidas
Breast Surgeon
Director of the HYGEIA Breast Center
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