What is triple-negative breast cancer and what are its pathological characteristics?

Breast cancer is a highly heterogeneous disease. Breast cancers of different molecular types have obvious differences in biological behavior, response to treatment, and prognosis. So what is triple-negative breast cancer?

What is triple-negative breast cancer?

Tumors have their own naming principles. Simply put, only malignant tumors of epithelial origin are called cancer. Therefore, as the name suggests, breast cancer is "an epithelial malignant tumor occurring in the breast." Tumors that meet this condition can be histologically divided into a series of subtypes, including invasive carcinoma of non-special type, invasive lobular carcinoma, tubular carcinoma, carcinoma with medullary features, and other malignant tumors such as epithelial and myoepithelial origin, according to the fourth edition of the breast tumor classification published by the World Health Organization in 2012.

As the research deepened, we found that the biological behavior of breast cancer is closely related to its molecular biological indicators, the most important of which are the status of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The different states of these three indicators can not only predict the patient's clinical biological behavior, but also guide the formulation of corresponding treatment plans. If ER and PR are positive, it means that the patient may benefit from endocrine therapy; and if HER2 is positive, it means that the patient may respond to trastuzumab treatment.

According to the different combinations of the status of these three indicators, different groupings appear, such as ER and/or PR positive, HER2 negative, ER and/or PR negative, HER2 positive, and all three negative (the so-called triple-negative breast cancer). If other molecular biological indicators such as epidermal growth factor receptor (EGFR), proliferation index, etc. are added, there will be more different combinations.

From this we can see that molecular classification and histological classification are two different classification methods, so the two cannot be directly equated.

The prognostic and predictive significance of various indicators in triple-negative breast cancer

Large-scale randomized clinical trials have confirmed that the prognostic value of ER is small, but it has a strong predictive effect on endocrine therapy (such as tamoxifen). Tamoxifen binds to ERα and inhibits the stimulatory effect of estrogen on tumor cell growth, which can significantly reduce cancer recurrence and prolong the survival of patients with ERα-positive invasive breast cancer of all stages.

PR expression levels are directly correlated with response to endocrine therapy, and even a small number of PR-positive tumor cells (≥1%) may have a significant response to endocrine therapy.

In the absence of systemic adjuvant therapy, patients with HER2-positive breast cancer have a poor prognosis, with high recurrence and mortality rates, which has significant adverse prognostic significance. In terms of treatment, HER2 positivity has predictive significance for anthracycline- and taxane-based treatment. Since the monoclonal antibody trastuzumab targeting HER2 was approved for the treatment of some breast cancers, HER2 testing has become more important in guiding treatment.

Overlap between triple-negative breast cancer and histological and other molecular biological classifications

As mentioned above, molecular classification and histological classification are two different classification methods, so there will be some overlap and intersection between the two. For example, in histological classification, carcinoma with medullary features and adenoid cystic carcinoma, although molecular classification shows triple negative, their risk of distant metastasis is relatively low. It is currently believed that axillary lymph node dissection is not necessary for the treatment of adenoid cystic carcinoma, and whether adjuvant therapy is used after surgery has little effect on the prognosis.

In addition to ER, PR, and HER2, there are many other molecular indicators in breast cancer, such as EGFR, cytokeratin (such as CK5/6, CK14, CK17), Ki-67, etc., which have led to many classifications. Among them, the basal subtype is worth mentioning. The definition of basal subtype refers to the expression of basal cell markers on the basis of triple negative. Although this type of tumor was discovered and named through gene expression spectrum research, it also has certain histological characteristics: higher histological grade, geographic necrosis, thin tumor borders, and lymphocyte reaction in the stroma. These morphologies overlap, to some extent, with carcinomas with myeloid features; however, this group of tumors has a poor prognosis and is insensitive to conventional chemotherapy regimens. Therefore, it is necessary to distinguish between the two accurately.

in conclusion

To sum up, "triple-negative" breast cancer is only one aspect of our observation of things. This alone can provide certain information, but it is far from enough for the treatment and prognosis of patients; it cannot even reach the level of "the final word".