October is now established as “Breast Cancer Prevention & Awareness Month”. One in eight women will at some point be diagnosed with breast cancer, while every year 4,500 women in our country are affected by the disease. Although the average age of diagnosis is 62 years, approximately 10% of patients are diagnosed before the age of 45. This means that a large proportion of patients are premenopausal, of reproductive age and professionally active.

Fortunately 66% of cases are diagnosed at an early stage where the disease is limited to the breast and the prognosis is excellent.

In recent years many developments have changed the therapeutic landscape and the prognosis of early breast cancer. The doctors of the therapeutic clinic (Alexandra Hospital) of the School of Medicine of EKPA Dr. Angeliki Andrikopoulou, Dr. Maria Kaparelou (Pathologist – Oncologist), Theodora Psaltopoulou (Pathologist, Professor of Therapeutics-Epidemiology-Preventive Medicine) and Thanos Dimopoulos (former Rector of EKPA, Professor of Therapeutics-Oncology-Hematology, Director of the Therapeutic Clinic) summarize the most important developments.

Initially, many women now with hormone-sensitive breast cancer, i.e. with disease that expresses the estrogenic and/or progesterone receptors, can avoid chemotherapy. This follows the widespread application of gene panels (“gene signatures”) that study the expression of genes in the tumor and have either a positive or negative prognostic role. Such panels are Oncotype, MammaPrint and Endopredict.

After the TAILORx and RxPONDER studies, the use of Oncotype in women with early hormone-sensitive HER2-negative breast cancer has helped to avoid treatment in a large proportion. In particular, postmenopausal women with early breast cancer, tumors up to 5 cm and up to 3 infiltrated lymph nodes (N1) with a score below 25 can avoid chemotherapy and receive only endocrine therapy.

Accordingly on premenopausal women, women with tumors up to 5 cm without positive lymph nodes and a score of less than 20 can avoid chemotherapy for the most part, and only patients with a score of more than 20 and with positive lymph nodes should definitely undergo chemotherapy. MammaPrint, respectively, is another gene panel used in postmenopausal women at high clinical risk. For those women with a low MammaPrint score, chemotherapy may be avoided. Based on these developments, the treatment plan was changed to avoid chemotherapy in 30% of patients compared to the initial estimate.

For women at high clinical risk with hormone-sensitive HER2-negative breast cancer, two new drugs in adjuvant therapy after surgery have further reduced the risk of recurrence. These are the inhibitors of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) abemaciclib (abemaciclib) and ribociclib (ribociclib). The MonarchE study continues even at 5 years to show a benefit of adjuvant ambemaciclib reducing the risk of relapse by 32% and increasing the percentage of patients who have not relapsed at 5 years by 7.6%. Accordingly, the NATALEE study continues at 4 years to show benefit from adjuvant ribociclib. Based on updated data announced at this year’s ESMO 2024 conference, the administration of ribociclib reduces the risk of recurrence by 28.5% in patients with stage II and III early hormone-sensitive breast cancer. Even in patients without positive lymph nodes, the benefit was significant from the administration of ribociclib (absolute benefit 5.1% at 4 years).

At the same time, new drugs that are now approved for adjuvant therapy are PARP protein inhibitors. Specifically, approximately 5-10% of breast cancer patients carry inherited mutations in the BRCA1 and BRCA2 genes.

This rate increases to 10% in women diagnosed under the age of 35, and increases even more in patients with a positive family history, bilateral breast cancer, or current/post-diagnosis of ovarian cancer. The OlympiA study showed benefit from the adjuvant administration of the PARP inhibitor olaparib (olaparib) in patients with high-risk hormone-sensitive and triple-negative breast cancer carrying mutations in the BRCA1/2 genes. Specifically, administration of olaparib for 1 year reduces the risk of death by 32%.

About 20% of breast cancer patients have the HER2 gene. The existence of this gene in a tumor is a growth factor of its cell proliferation as well as a factor of increased metastatic capacity. And for these patients, the developments are many compared to the older clinical practice. Patients with tumors larger than 2 cm (T2) or with lymph nodes should receive neoadjuvant chemotherapy in combination with therapy targeting the HER2 receptor and then be taken to surgery.

The maximum goal is that of a complete pathological response, that is, the elimination of the disease, as patients who achieve this have a better prognosis. Patients with HER2-positive early breast cancer achieve a pathologic complete response in 40-60% with higher rates in patients who do not express hormone receptors. Adjuvant therapy with an antibody-drug conjugate, which contains the HER2-targeting antibody trastuzumab linked to a microtubule inhibitor, DM1, is now approved in the adjuvant treatment of patients who do not achieve a complete response. It is trastuzumab emtansine that showed continued benefit in terms of relapse (46%) as it reduced the percentage of patients who had relapsed at 8.4 years from 32.2% to 19.7%. Therefore, the now standard practice of adjuvant trastuzumab with pertuzumab for one year is being changed and replaced by trastuzumab emtansine in patients who have not achieved a complete response to neoadjuvant therapy.

And practice for triple-negative breast cancer has changed in recent years. Patients with tumors >2 cm (T2) or with positive lymph nodes now receive neoadjuvant chemotherapy in combination with pembrolizumab immunotherapy. At the ESMO 2024 conference, data from the KEYNOTE-522 study were announced. Combining pembrolizumab immunotherapy with anthracycline and taxane chemotherapy reduced the risk of death by 34% but also increased the complete response rate from 51.2% to 64.8%. Now, neoadjuvant chemotherapy with immunotherapy has been established in triple-negative breast cancer. In those cases where a complete disease response has been achieved, patients receive another 9 cycles of immunotherapy with adjuvant pembrolizumab. In cases where there is no complete response, adjuvant chemotherapy with capecitabine is given for 6 months based on the CREATE-X study. However, a special category are patients who carry mutations in the BRCA1/2 genes, which constitute 15 – 25% of patients with triple negative breast cancer. These patients will receive adjuvant treatment with olaparib based on the Olympia study. The treatment landscape of early breast cancer has changed dramatically in recent years and will continue to change with the adoption of new drugs.