Background

Perou et al. (2000) first proposed breast cancer molecules based on cDNA gene chip technology. Before that, basal cell like breast cancer (BLBC) was defined as a kind of breast cancer that showed myoepithelial cell differentiation. With the gradual promotion of molecular classification of breast cancer, BLBC has been recognized as an independent subtype with different biological behaviors and clinical prognosis (Perou et al., 2000). BLBC is a kind of breast malignant tumor with large heterogeneity, high malignancy and poor prognosis. In clinical diagnosis, it is easily confused with the general type of triple negative breast cancer (TNBC). BLBC has high proliferative index and poor clinical prognosis and with few treatment. This paper summarizes the related characteristics and treatment methods of BLBC (Yang et al., 2015).

1 Epidemiology

Breast cancer is the most common malignant tumor that causes the death of women. BLBC accounts for about 10 to 20. 8 percent of all breast cancers, and is the most common in premenopausal women of African descent (only 40 percent in postmenopausal women). The results suggest that there may be some racial and age differences in the occurrence of BLBC. There are few studies on BLBC among the yellow race, and the incidence of BLBC in China is between 10 and 17. 4%, which is the same as the common account (Carey et al., 2006; Milioli et al., 2017) BLBC is characterized by early onset age (less than 50 years) and poor prognosis.

2 Pathological Characteristics

2.1 Histologic characteristics

The histological classification was mostly invasive ductal carcinoma, and the histological grade was mostly III grade. The tumor tissue was composed of solid nesting lamellar structure and had pushing edge. In the center of cancer tissue, there were acellular scar area, map like flake necrosis area, and different degree of lymphocyte infiltration in interstitial tissue. The tumor cells were syncytic with unclear boundaries, the nuclei were vacuolated, the nucleoli were often visible, and the mitotic appearance was more frequent (Lo et al., 2016).

2.2 Biomarker characteristics

2.2.1 Estrogen receptors (ER), progesterone receptors (PR) and ER-2

BLBC is a subtype of molecular typing of breast cancer which is identified according to gene expression profiles so they have similar or identical gene expression profiles. According to the study of gene map, the ERPRHER-2 expression of most BLBC is negative, that is to say, the majority of BLBC belongs to triple negative breast cancer (triple-negative breast carcinoma TNBC).

2.2.2 Ki-67

Ki-67, as a recognized marker of cell proliferation activity, may play an important role in promoting the metastasis of BLBC. In basal cell-like breast cancer, Ki-67 is strongly expressed in the nucleus, and when it is in higher cases, it suggests that axillary lymph node metastasis may exist (Zhao et al., 2016; Bedi et al., 2017; Megan et al., 2017).

2.2.3 C-Myc

C-Myc genes are more likely to be amplified and expressed in ER negative patients (Park et al., 2018).

2.2.4 P53

The positive rate of p53 in BLBC was significantly higher than that in normal mammary tissue, which indicated that the expression of p53 in BLBC was enhanced. As a result, the apoptosis of tumor cells was inhibited, and the development of tumor was promoted (Gracio et al., 2017).

2.2.5 FOXM1 and Slug

By inhibiting the expression of E-cadherin and promoting the expression of vinmentin, FOXM1 and Slug promoted the local invasion and distant metastasis of BLBC, and they can be used as a prognostic index of BLBC (Payandeh et al., 2016; Zhou et al., 2016).

3 Clinical Features

The characteristics of BLBC are early onset (mostly less than 50 years old) and most of the mass size concentrated in 2-5 cm, which has no significant characteristics. BCBL is different from other subtype of breast cancer in biological behavior and case characteristics, and with higher grade in histological. Most of the patients are with negative lymph nodes and early clinical stage, but it is easy to be found invasion in clinical, and with high recurrence rate and short survival .What’s more, BLBC has a special metastasis pathway, which is easy to metastasize to brain and visceral organs, besides to bone (Klemm et al., 2011; Shao et al., 2013; Ren et al., 2016). Basal cell-like breast cancer may be divided into two subtypes: one is aggressive and prone to early recurrence and metastasis; The other, despite its invasive histological features, it does not recur. The classify suggesting that basal cell-like breast cancer may also have heterogeneity (Fulford et al., 2007; Liu et al., 2012; Adamo et al., 2017; Milioli et al., 2017).

4 Diagnose

4.1 Clinical diagnosis

The traditional diagnosis of BLBC requires patients to detect gene maps, but because of the cost and the feasibility of clinical operation, gene mapping is difficult to become a routine clinical detection means, therefore, the clinical diagnoses of basal cell-like breast cancer are mostly based on immunohistochemical results.

Most of the immunohistochemical results of BLBC were tri-negative, but some studies showed that compared with the immunohistochemical phenotype of ER/PR/HER-2. But it is showed that it is necessary to check the impression of CK5/6 and EGFR. If more than one of CK5/6 and EGFR were positive expression, the diagnosis rate of basal cell-like breast cancer can be improved and the prediction of the prognosis of breast cancer patients could be better (Parada et al., 2017). Most people believe that CK5/6 is the most effective marker for the diagnosis of BLBC, but some CK5/6 negative basal cell-like breast cancer is positive for CK14 and CK17 expression. Therefore, in suspected cases, the combined use of the three can be considered (Maggie et al., 2008). To draw a conclusion, the current clinical definition of BLBC is that ER, PR, Her-2 are negative with at least one of the basal cell keratin and (or) myoepithelial marker CK5/6, P63, CD10 positive expression. BLBC is a subtype of invasive carcinoma (Adamo et al., 2017).

4.2 Antidiastole

Triple negative breast cancer is a kind of breast cancer with the same characteristics in immunohistochemical staining. In immunohistochemical staining, estrogen receptor ER, progesterone receptor PR, human epidermal growth factor receptor HER-2, is negative at the same time. It can be divided into basal cell-like subtype, mesenchymal stem cell subtype, immunomodulatory subtype, androgen subtype (Parada et al., 2017). But triple negative breast cancer may also be a normal breast-like type on the genetic map (Sanz et al., 2016).

By genetic map analysis, about 15% of the BLBC expressed ERPRHER-2 in varying degrees. Only 56-84% of TNBC cases expressed basal keratin, myoepithelial cell labeling and EGFR. The relationship between BLBC and TNBC was mostly crossed, but not completely overlapped (Badowskakozakiewicz et al., 2016; Hoadley et al., 2016).

5 Treatment

5.1 Local treatment

Surgery is the best choice for local control. Although some scholars believe that BLBC has a high local recurrence rate, clinical experiments have proved that there are similar local recurrence rates in breast conserving surgery and mastectomy. Breast conserving surgery is still advocated for early BLBC, because of its minor trauma (Lehanm et al., 2011).

5.2 Traditional systemic therapy

At present, there are no definite targets for endocrine therapy and targeted therapy. Chemotherapy is the only effective systemic therapy, but BLBC is not sensitive to conventional chemotherapeutic drugs, the effect of chemotherapeutic drugs is limited, and the prognosis is poor.

5.3 New targeted therapy

Once chemotherapeutic drug resistance occurs in patients with BLBC, the consequences are generally catastrophic, and recurrence and metastasis occur rapidly. In order to increase the choice of treatment options and improve the prognosis of patients, a large number of researchers have done a lot of research in the direction of targeted treatment. Although no targeted drug for BLBC has been certified by FDA, a variety of targeted drugs have entered the clinical trial stage, providing more possibilities for targeted treatment of BLBC (Ishitha et al., 2016).

5.3.1 Targeted therapy for DNA repair

It mainly includes Poly ADP-ribose Polymerase (PARP) inhibitors and platinum drugs.

PARP inhibitors result in cell death by consistently blocking the formation of adenosine ribose polymers, known as the “synthetic lethal” principle. At present, we have entered the phase of clinical trial of II. The main research includes single drug therapy and combined drug therapy, in which olapanil and chemotherapeutic drugs have achieved a high objective response rate in clinical trials. But its mechanism of inhibiting DNA repair increases the risk of a second primary tumor (Bauer et al., 2007; Xu et al., 2017).

Platinum drugs are a classical chemotherapeutic drug, which can restrict the release and replication of DNA and exert its antitumor effect. BLBC with BRCA-1 mutation is sensitive to platinum drugs, and its anticancer mechanism is similar to that of targeted therapy (Chaudhuri et al., 2016).

5.3.2 Targeted therapy related to tyrosine kinase (tyrosine kinase) inhibitors

Human epidermal growth factor receptor (EGFR): EGFR can promote tumor cell proliferation, invasion, metastasis and angiogenesis. The overexpression of EGFR in BLBC makes it a potential therapy for BLBC. Although clinical studies show that EGFR inhibitors alone are difficult to achieve the purpose of anti-tumor, EGFR inhibitors may be more suitable as a class of sensitizers to use (Krüger et al., 2017).

Vascular endothelial growth factor (VEFG): bevacizumab is the only anti-angiogenic agent for metastatic mammary glands approved by FDA, but FDA withdrew its indications for breast cancer in 2011. Because many III phase clinical trials showed the addition of bevacizumab on the basis of docetaxel chemotherapy did not improve the PFS and OS of breast cancer patients, but the toxicity was obviously increased.

C-Met Pathway: some studies have shown that the activation of c-Met pathway is related to the progression of breast cancer, especially BLBC and TNBC. Therefore, continuous inhibition of c-Met pathway will be one of the basic treatments to control the progression of breast cancer (Tutt et al., 2012; Ho-Yen et al., 2014).

5.4 New endocrine therapym

Breast cancer with overexpression of androgen receptor (AR) is a kind of breast cancer with unique prognosis. Overexpression of AR often indicates poor prognosis. Blocking the expression of AR is a feasible endocrine therapy for BLBC. It is gradually becoming a hot research (Samol et al., 2012).

6 Expectation

Current studies of the treatment of BLBC focus on: DNA repair defects, targeted therapy associated with tyrosine kinase inhibitors, immune-related, androgen receptor overexpression, although most studies have explored the genetic map of BLBC. However, it is still difficult to give effective targeted therapy in clinic (Colan et al., 2015; Jung et al., 2015). Looking for a new marker of basal cell like breast cancer, aiming to improve the total survival time of patients, will become a new direction for the treatment of basal cell like breast cancer in the future.

Authors’ contributions

JYZ wrote this manuscript. DWZ revised the manuscript. All authors read and approved the final manuscript.

Acknowledgments

This work was supported by the Heilongjiang scientific research project (grants 201810).

References

Adamo B., Ricciardi G.R.R., Ieni A., et al., 2017, The prognostic significance of combined androgen receptor, E-Cadherin, Ki67 and CK5/6 expression in patients with triple negative breast cancer, Oncotarget, 8(44): 76974-76986

https://doi.org/10.18632/oncotarget.20293

PMid:29100362 PMCid:PMC5652756

Bedi D., Vig K., Waduwawara S., Samant R.S., et al., 2017, Gene signature for predicting worse relapse-free survival with basal-like breast cancer, Research Reports, 10003, e1-e12

Badowskakozakiewicz A.M., and Budzik M.P., 2016, Immunohistochemical characteristics of basal-like breast cancer, Contemporary Oncology, 20(6): 436

Bauer K.R., Brown M., Cress R.D., et al., 2007, Descriptive analysis of estrogen receptor-negative, progesterone receptor-negative, and Her-2-negative breast cancer, the so-called triple-negative phenotype: a population-based study from the California Cancer Registry, Cancer, 109(9): 1721-1728

https://doi.org/10.1002/cncr.22618

PMid:17387718

Carey L.A., Perou C.M., Livasy C.A., et al., 2006, Race, Breast Cancer subtype, and survival in the Carolina Breast Cancer Study, JAMA, 295(21): 2492-2502

https://doi.org/10.1001/jama.295.21.2492

PMid:16757721

Chaudhuri G., and Misra S., 2016, Abstract 4587: Dynactin dysregulation-induced increase inEGFR on basal-like breastcancer cells, Cancer Research, 76(14): 4587-4587

https://doi.org/10.1158/1538-7445.AM2016-4587

Colan M. HoYen, J. Louise Jones, and Stephanie K., 2015, The Clinal and functional significance of c-Met in breast cancer: a review, Breast Cancer Research, 17: 52

https://doi.org/10.1186/s13058-015-0547-6

PMid:25887320 PMCid:PMC4389345

Fulford L.G., Reis-Filho J.S., Ryder K., et al., 2007, Basal-like Grade III invasive ductal caicinoma of the breast: patterns of metastasis and long-term survival, Breast Cancer Res, 9(1): R4.10

Gracio F., Burford B., Gazinska P., et al., 2017, Splicing imbalances in basal-like breast cancer underpin perturbation of cell surface and oncogenic pathways and are associated with patients’ survival, Scientific Repprt, 7: 40177

https://doi.org/10.1038/srep40177

PMid:28059167 PMCid:PMC5216415

Hoadley K.A., Siegel M.B., and Kanchi K.L., 2016, Tumor evolution in two patients with basal-like breast cancer: A retrospective genomics study of multiple metastases, Plos Medicine, 14(1): e1002174

https://doi.org/10.1371/journal.pmed.1002174

PMid:27923045 PMCid:PMC5140046

Ho-Yen C.M., Green A.R., Rakha E.A., et al., 2014, C-Met in invasive breast cancer: is there a relationship with the basal-like subtype, Cancer, 120(2): 163-71

https://doi.org/10.1002/cncr.28386

Ishitha G., Manipadam M.T., Backianathan S., et al., 2016, Clinicopathological study of triple negative breast cancers, Journal of Clinical and Diagnostic Research, 10(9): EC05-9

https://doi.org/10.7860/JCDR/2016/20475.8539

Choi J.E., Kang S.H., Lee S.J., et al., 2015, Androgen receptor expression predicts decreased survival in early stage triple-negative breast cancer, Surgical Oncology, 22: 82-89

https://doi.org/10.1245/s10434-014-3984-z

PMid:25145503

Klemm F., Bleckmann A., Siam L., et al., 2011, β-catenin-independent WHT signaling in basal-like breast cancer and brain metastasis, Advance Access, 32(3): 434-442

https://doi.org/10.1038/s41598-017-00862-w

PMid:28439082 PMCid:PMC5430803

Krüger K., Wik E., Knutsvik G., et al., 2017, Expression of Nest in associates with BRCA1 mutations, a basal-like phenotype and aggressive breast cancer, Scientific Reports, 7(1):1089-1096

Liu S.Z., Lachapelle J., Leung S., et al., 2012, CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer, Breast Cancer Research, 14: R48.54

Lehanm B.D., Bauer J.A., Chen X., et al., 2011, Identification of human Triple-negative cancer subtype and preclincial models for section of tarfeted therapies, The Journal of Clinical Investigation, 121(7): 2750-2767

https://doi.org/10.1172/JCI45014

PMid:21633166 PMCid:PMC3127435

Lo P.K., Wolfson B., and Zhou Q., 2016, Cancer stem cells and early stage basal-like breast cancer, World Journal of Obstetrics & Gynecology, 5(2): 150

https://doi.org/10.5317/wjog.v5.i2.150

PMid:28239564 PMCid:PMC5321620

Milioli H.H., Tishchenko I., Riveros C., et al., 2017, Basal-like breast cancer: molecular profiles, clinical features and survival outcomes, Bmc Medical Genomics, 10(1): 19

https://doi.org/10.1186/s12920-017-0250-9

PMid:28351365 PMCid:PMC5370447

Megan A. Healey, Kelly A. Hirko, Andrew H. Beck., et al., 2017, Assessment of Ki67 expression for breast cancer subtype classification and prognosis in the Nurses’ Health Study, Breast Cancer Res Treat, November Volume 166, Issue 2, pp.613-622

Milioli H.H., Tishchenko I., Riveros C., et al., 2017, Basal-like breast cancer: molecular profiles, clinical features and survival outcomes, Bmc Medical Genomics, 10(1): 19

https://doi.org/10.1186/s12920-017-0250-9

PMid:28351365 PMCid:PMC5370447

Maggie C.U. Cheang, David Voduc, Chris Bajdik, et al., 2008, Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotye, Clincial Cancer Research, 14(5): 1368-1376

https://doi.org/10.1158/1078-0432.CCR-07-1658

PMid:18316557

Perou C.M., Sorlie T., Eisen M.B., et al., 2000, Molecular portraits of human breast tumours, Nature, 406(6797): 747-752

https://doi.org/10.1038/35021093

PMid:10963602

Park K.U., Chen Y., Chitale D., et al., 2018, Utilization of the 21-gene recurrence score in a diverse breast cancer patient population: development of a clinicopathologic model to predict high-risk scores and response to neoadjuvant chemotherapy, Analysis of Surgical Oncology, (20): pp.1-7

Parada H., Sun X., Fleming J.M., et al., 2017, Race-associated biological differences among luminal A and basal-likebreast cancers in the Carolina breast cancer study, Breast Cancer Research, 19(1): 131

https://doi.org/10.1186/s13058-017-0914-6

PMid:29228969 PMCid:PMC5725885

Payandeh M., Sadeghi M., Sadeghi E., et al., 2016, Expression of p53 breast cancer in Kurdish women in the west of Iran: a reverse correlation with lymph node metastasis, Asian Pacific Journal of Cancer Prevention, 17(3): 1261

https://doi.org/10.7314/APJCP.2016.17.3.1261

PMid:27039757

Qian-Qian X.U., Wang C.J., Sun Q., et al., 2017, Triple-negative breast cancer: molecular subtypes and individual targeted therapies, Chinese journal of cancer prevention, 24(11): 788-794

rSanz J.S., Sánchez M.T.O., Campos J.E., et al., 2016, Immunohistochemistry for triple-negative breast cancer, Methods in Molecular Biology, 1406(1): 39

Ren X., Yuan L., Shen S., et al., 2016, c-Met and ERβ expression differences in basal-like and non-basal-like triple-negative breast cancer, Tumor Biology, 37(8): 11385-11395

https://doi.org/10.1007/s13277-016-5010-5

PMid:26968553

Shao Z.M., 2013, Tumor of the breast, Fudan Publishing House, 300-301

Samol J., Ranson M., Scott E., et al., 2012, Safety and tolerability of the poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib (AZD2281) in combination with topote can for the treatment of patient with advanced solid tumors: a phase I study , Invest New Drugs, 30(4): 1493-1500

https://doi.org/10.1007/s10637-011-9682-9

PMid:21590367

Tutt A., Robson M., Garber J.E., et al., 2012, Prevalence BRCA mutations in an unselected population of Triple-negative breast cancer, Cancer, 118(11): 2787-2795

https://doi.org/10.1002/cncr.26576

PMid:22614657

Yang Longan, et al., 2015, The clinical pathological features analysis of basal-like breast cancer and triple negative breast cancer, Jiangsu medicine, 41(20): 2404-2406

Zhao X.T., Sun J., and Wang C.F., 2016, The medical certificate of Ki-67in basal-like breast cancer, Chinese Journal of histochemistry and cytochemistry, 25(5): 426-430

Zhou W., Ni T., Wronski A., et al., 2016, The SIRT2 deacetylase stabilizes slug to control malignancy of basal-like breast cancer, cell reports, 17(5): 1302

https://doi.org/10.1016/j.celrep.2016.10.006

PMid:27783945 PMCid:PMC5108094