An analysis of the relationship between breast cancer resistance protein BCRP and breast cancer

 Breast cancer is a common malignancy in women, and multidrug resistance is one of the main reasons affecting the efficacy of chemotherapy and patient survival in breast cancer. A tumor drug resistance-associated protein, BCRP, has been reported in breast cancer drug-resistant cell lines. 

Also, BCRP is a transporter, mainly responsible for the excretion of endogenous and exogenous substances outside the cell, and has a vital role in drug metabolism research.

The BCRP gene of human breast cancer resistance protein (BCRP) is located in the chromosome 4q22 region. It encodes 655 amino acids, which are present in several vital organs in the body, such as the small intestine, placenta, liver, and kidney. It is essential for drug absorption, distribution, metabolism, and excretion. Drug transport proteins play a vital role in drug metabolism kinetics. According to the drug transport mode, drug transport proteins can be divided into drug uptake proteins and drug efflux proteins. 

As a member of the ABC transporter family, BCRP is the 3rd largest efflux transporter protein identified after P-GP and MRP1 resistance proteins, so it can efflux certain drugs entering cells and reduce intracellular drug concentrations, resulting in effects such as drug resistance, diminished drug action, and enhanced drug toxicity.

1, The relationship between BCRP and breast cancer.

BCRP is widely distributed in the body and has a variety of substrates, which is an essential factor in causing drug resistance of oncological chemotherapy drugs but also affects the in vivo process of non-anti-cancer other medicines. BCRP can increase the entry of drugs or foreign chemical substances into the mammary gland. One study found that the plasma/milk ratio of acyclovir was 5:1 in wild-type mice. 

In contrast, the mammary accumulation of acyclovir was significantly lower in Abcg2-/-mice, and similarly, the BCRP transporter can increase the uptake of cimetidine, furantoin, and PhIP in the mammary gland. Abnormal expression of BCRP can promote the excretion of anticancer drugs from cancer cell membranes, leading to a decrease in the biological activity of anticancer drugs, which in turn stimulates the tolerance of cancer cells to the drugs.

BCRP has a vital role in pharmacokinetics by enhancing the activity of ATP-dependent transporter proteins in cell membranes, which promotes the efflux of anticancer drugs through transporter proteins in cell membranes and enhances their drug resistance. It has also been found that BCRP can improve the tolerance of cancer tissues to anticancer drugs by inducing abnormal cell cycle regulation in cancer cells, which in turn promotes the development and progression of breast cancer. 

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It has been shown that BCRP is associated with clinical chemotherapy sensitivity in various tumors, and the expression of BCRP is upregulated in patients treated with multiple chemotherapies, suggesting that chemotherapeutic drugs induce the expression of BCRP. In contrast, high expression of BCRP leads to the development of clinical drug resistance.

2, Predictive value of BCRP on the efficacy of neoadjuvant therapy for breast cancer

Neoadjuvant chemotherapy, also known as preoperative chemotherapy, induction chemotherapy, or initial chemotherapy, refers to systemic and systemic cytotoxic drug therapy given to non-metastatic tumors before the application of surgery or radiotherapy.

 Some investigators investigated the changes in breast cancer resistance protein (BCRP) expression before and after neoadjuvant chemotherapy and its relationship with chemotherapeutic efficacy to evaluate the predictive value of BCRP on neoadjuvant chemotherapeutic effectiveness [1]. The method was to apply immunohistochemistry to detect the expression of BCRP in cancer tissues before and after neoadjuvant chemotherapy in the same breast cancer case and analyze its relationship with neoadjuvant chemotherapy efficacy and clinicopathological indexes. 

 Results:

(1) The positive expression rate of BCRP before neoadjuvant chemotherapy was 52. 3%, and the difference between its expression after and before chemotherapy was statistically significant (P<0.05).

(2) The positive expression rate of BCRP before chemotherapy in the influential group after neoadjuvant chemotherapy was lower than that in the ineffective group, and the difference was statistically significant (P<0.05).

(3) The positive expression rate of BCRP was highest in the HER-2-positive group, and the difference was statistically significant compared with the Luminal type and triple-negative type (P<0.05).

(4) The positive expression rate of BCRP was significantly higher in the axillary lymph node metastasis group than in the no lymph node metastasis group (P<0.05).

Therefore, the expression of BCRP has some changes before and after neoadjuvant chemotherapy. Its expression level is related to the clinical efficacy and clinicopathological index of neoadjuvant chemotherapy, which has predictive value for the effectiveness of neoadjuvant therapy for breast cancer. 

ABC transporter protein has an important role in drug metabolism kinetics. It is the most critical molecule mediating multidrug resistance, among which the more substantial the expression and activity of BCRP, the stronger the efflux effect on cytotoxic drugs. As a drug-resistance protein, in the future, people need to strengthen the research on the mechanism of action of BCRP, its mode of action, and the significance of its expression in human tissues, as well as in-depth research on its role in drug-resistant tumors and how to detect and reverse it.

[1] Correlation between the expression of breast cancer resistance proteins in breast cancer tissues and the efficacy of neoadjuvant chemotherapy [J].