Mammary tumors are in the process of re-cataloging. The landing of biological therapies against precise alterations requires that the rates are now grouped according to these molecular features and pathologic features of its cells, as did formerly. The continuing advances in research make the new scheme is provisional and could be improved.
The advent of molecular biology techniques has shattered the traditional classification of the different types of breast cancers, which served pathological characteristics of the cells. “I no longer grouped by appearance, but in terms of molecular alterations that would indicate a specific treatment,” summed Ramon Colomer, president-elect of the Spanish Society of Medical Oncology and Head of Service of the Catalan Institute of Oncology (ICO), Gerona.
Until recently breast tumors were considered ductal (80 percent) or lobular (12-14 percent), based on the morphology of the cells indicating either origin within the breast. But in the last five years, and by immunohistochemical techniques, we have seen that there can be more precise classifications tuned handling.
So far, three determinations decide therapy: state of estrogen receptors and progesterone receptors and the oncogene HER2 positivity.
These tests redefine the types of mammary tumors. The largest group of carcinomas would luminal be characterized by hormonally either the estrogen receptor, the progesterone or both.
The second major group would form some old acquaintances, tumors with HER2 positivity.
Third would be a catch for the moment is called a “provisional practice and” triple negative, positive or not get it for her 2 or for hormone receptors. The fourth and last group is called luminal type B and what are the hormone-receptor-negative progesterone.
The new division allows therapeutic decisions more appropriate to current knowledge, but “is still working to perfect it,” he explained Colomer.
tumors that are positive for a hormone receptor, either the estrogen, the progesterone or both, accounting for two thirds of the total and are called luminal, a feature of their cells.
The good response of these tumors to hormone therapy confers a favorable prognosis, especially since the arrival of the aromatase inhibitors, “which generally perform better and with fewer side effects than tamoxifen,” he noted Ramon Colomer.
However, tamoxifen, hormone par excellence, still has its role in the therapeutic arsenal of luminal tumors, “but now we try to clarify when entering, what is the best sequence of therapy.”
By custom, hormonal agents were administered after always relevant courses of chemotherapy, but “not because they were less effective, but because we are used to give a treat after another, and chemotherapy is shorter in time.” Now, several studies trying to determine what the best sequential scheme.
A tamoxifen, aromatase inhibitors (exemestane, letrozole and anastrozole) are now added raloxifene, a drug which is postmenopausal osteoporosis indication, but which has a structure similar to that of tamoxifen and has shown efficacy and fewer side effects in the breast cancer treatment, but has not yet gotten the indication.
HER2 Ni or estrogen or progesterone. Tumors that do not express any of these three receptors have been called so obvious and provisional, triple negative, until it is a trait that characterizes molecular. The triple negative “are a clear area of development because it is not clear what is the best treatment for them,” acknowledged Colomer.
Although there are a large percentage (just under 15 percent), hitherto known for their poor prognosis. Of them are known to be very sensitive to chemotherapy, but also that very soon become unresponsive.
The lack of a clear therapeutic option is spurring many clinical trials in this subgroup.As one of its features is that they exhibit the biological factor receptor (EGFR) altered, they test the anti EGFR monoclonal antibody cetuximab.
And, as well, have also altered other receptors, are testing the efficacy of biological therapies generation multifunction as sunitinib, an oral drug (already approved by the U.S. FDA for kidney cancer, leukemia and tumors refractory GIST) that simultaneously inhibits multiple tyrosine kinase receptors involved in tumor growth, angiogenesis and metastatic progression. Another candidate is the antiangiogenic drug bevacizumab, which selectively inhibits the vascular endothelial growth factor, also altered in this type of tumor.
treatments Besides the pointers are investigating whether some chemotherapy regimens are more appropriate than the more standard anthracycline taxane. In this respect, cisplatin is being tested, not normally used in breast cancer.
Her 2 positive
The head and tail of the breast cancers represent tumors are positive for HER2 receptor (just over 20 percent of the total). On one hand, the fact that express this receptor confers aggressiveness, but otherwise, have a pair of specifically targeted therapies that inhibit HER 2, control tumor growth and high cure rates obtained.
Current treatment is combination chemotherapy concurrently with the monoclonal antibody trastuzumab, directed specifically to block HER 2. This partnership has proven to be the most effective first line.
But the advent of biological therapy, lapatinib, which strengthens and expands the scope of trastuzumab, may further improve the prognosis of these ill. Lapatinib is a tyrosine kinase inhibitor of several HER receptors, including 2, administered orally, will initially be indicated for cases refractory to trastuzumab, although there is evidence that many of the combination results obtained trastuzumab-lapatinib extraordinarily good.
Finally, for HER2-positive tumors that also have hormone receptor-positive (less than 10 percent of cases), shortly adopt a combination of aromatase inhibitor plus trastuzumab, as it improves the results of hormone in lonely as Tandem study results, presented at the last congress of the European Society for Medical Oncology (ESMO) and involving the Colomer Group.
Type B luminal
Among all the hormone-dependent tumors, a small percentage (which ranges between 5 and 10 percent of this subgroup) having no positive progesterone receptor. “These few cases tend to respond to hormonal treatment and worse in the new classification is separating them from the rest and naming luminal type B,” said Ramon Colomer.
The latter group also represents a clear area of research, such as the triple negative. Currently, specific studies aimed at this subgroup in which we investigate whether there is any hormonal treatment to be better than another.Chemotherapy same for everyone Regardless of the type in which frame the tumor, chemotherapy, provided it is indicated , is the same. The current standard in breast cancer is based on a taxane and an anthracycline. The indication of chemotherapy is based more on the old classification (not needed tumors less than 1 cm in diameter and without lymph node is either surgically resected). Today 90 percent of the cases are still needing her. For triple negative tumors is investigated whether other cytostatic agents such as cisplatin, are best option.