Newer Approach to Triple Negative Breast Cancer
Treating triple negative breast cancer (TNBC) is a little difficult in comparison to breast cancers positive for receptors, in the sense that tamoxifen group of drugs does not have any effect on those cancers. These cancers are aggressive in nature and found in younger ladies.
A breast cancer can be positive for estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor (HER2). When a breast cancer is negative for these receptors, it is categorized as triple negative breast cancer.
There are drugs that can block the receptors in receptor positive breast cancers, but act on the receptor negative cases. Those can be tamoxifen group of drugs and trastuzumab.
Now, researchers from Dublin (Ireland) found that TNBC express epidermal growth factor receptor (EGFR) in abundance. They targeted enzymes called ADAMs (a disintegrin and metalloprotease), those required for activation of EGFR binding proteins during the signaling process. Gefitinib, a drug that inhibits EGFR was put to the test along with ADAM17 inhibitor, but the compound worked in isolation, before the treatment with EGFR inhibitors to a fair extent, but did not help in combination with EGFR inhibitors.
Later on they tried another unnamed drug which blocks ADAM10 and ADAM17 and found good response in about 91% of cases. They found the treatment of TNBC cells line with this compound reduced their ability to migrate, a process that is vital for the progression of cancer
There are at least four types of epidermal growth factor receptors, namely: EGFR, HER2, HER3 and HER4. Triple negative breast cancers comprise 10-20% of all breast cancer cases.
Women with TNBC tend to present with;
- higher grade,
- larger tumors,
- younger age at diagnosis,
- have a higher incidence of metastases
and
- have a shorter time to recurrence compared to other breast cancer types.
One reason for the poor prognosis for this group is the lack of targeted therapies in addition to surgery and chemotherapy.
Having found that an ADAM inhibitor can reduce the proliferation of TNBC cell lines, they hope that ADAMs may be a useful therapeutic target.
Perhaps the days are not far away when triple negative breast cancer will respond as nicely as breast cancers positive for ER, PR and HER2.
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