HER2 amplification is widely utilized as molecular markers for trastuzumab target treatment. Hence, analysis of HER2/neu expression on breast tissue is used as the standard of care now [8]. The HER2 gene encodes a transmembrane tyrosine kinase receptor (the human epidermal growth factor receptor). It is located on 17q21.1, which encodes two oncogenes. Most recently, a series of HER2-targeting agents were developed, including trastuzumab, pertuzumab, ertumaxomab, and lapatinib. HER2 gene amplification or protein overexpression is demonstrated in approximately 25 % of newly diagnosed breast cancers. HER2/neu gene amplification is associated with a worse prognosis in patients with node-positive breast cancer due to increased proliferation and angiogenesis and inhibition of apoptosis [9, 10].

Even though the incidence and importance of HER2 amplification in lobular carcinoma are less than that in ductal carcinoma, the HER2 amplification is still an important adverse prognostic factor in lobular breast cancer [11]. It is suggested that tumor-initiating cells (side population fraction by cytometry, SP) of breast cancer present important HER2 expression—the SP fraction was reduced by HER2 inhibitors [12]. A meta-analysis for cohort randomized trials on women with HER2-positive early breast cancer explored that trastuzumab-based adjuvant chemotherapy derived profit in disease-free survival, overall survival, and recurrence to adjuvant chemotherapy [13]. The candidate gene is regarded as amplification when demonstrating more than six HER2 copies per nucleus or with a ratio of HER2 to centromere 17 greater than 2.2. The HER2 amplification and overexpression have been associated with negative responses to conventional chemotherapy and poor prognosis, but better overall survival rate for trastuzumab in breast cancer [14, 15].

DNA topoisomerase II alpha (TOP2A) is a new marker of cell cycle turnover. TOP2A gene is located on chromosome 17q21-q22. TOP2A is a major target of anthracycline activity [16]. In breast cancer, TOP2A expression has been associated with HER2 protein overexpression and cell proliferation.

The TOP2A gene showed an increase in responsiveness to anthracycline-containing chemotherapy modalities relative to non-anthracycline regimens [17]. Because the gene locus of TOP2A is fairly close to the HER2 gene, the amplification of TOP2A is often cooperated with HER2 gene amplification. Twenty-three patients with T2–T4 ER-negative and HER2-overexpressed breast cancers treated with anthracycline-based chemotherapy were evaluated by Orlando et al. TOP2A was amplified in five (22 %) of the tumors. In all patients with TOP2A amplification, HER2 gene amplification was determined as well. It was reported that the pathological complete remission ratio in TOP2A amplified tumors is higher than in tumors without TOP2A amplification (respectively, 60 % and 15 %). It is postulated that in endocrine-unresponsive/HER2 overexpression cases, TOP2A amplification or the polysomy of chromosome 17 is associated with meaningfully high remission after anthracycline-based chemotherapy [18]. TOP2A is used as a molecular target of anthracycline drug and is pretty helpful as a predictive marker of response to anthracycline therapy [19].

TAU is one of the microtubule-associated proteins (MAPs) and is located on chromosome 17q21.1. Tubulin-targeting agents alter the microtubule function to disrupt cell shape, spindle formation, and microvesicle transportation. Detection of TAU expression may direct doctors to choose the patients who are likely to benefit more from taxane treatment. The decreased expression of TAU is accompanied with high responsiveness to paclitaxel in vitro. TAU enhances microtubule assembly and stabilizes microtubules and it is likely that TAU competes with taxanes for microtubule binding [20, 21]. It was shown that high TAU mRNA expression in ER-positive breast cancer presented as endocrine-sensitive but chemotherapy-resistant. On the contrary, low TAU expression in ER-positive cancers presented a poor prognosis with tamoxifen alone, but may profit from taxane-containing chemotherapy [22]. Patients with TAU-negative expression showed better response to paclitaxel administration compared to patients with TAU-positive expression (respectively, 60 % and 15 %) [23]. Amplified TOP2A and TAU genes are correlated to an important response to anthracycline-based chemotherapy, taxane, or cisplatin, respectively.

The breast cancer predisposition gene BRCA1 is located on chromosome 17q12-21. The breast cancer genes BRCA1 and BRCA2 are involved in tumor suppressor pathways, such as DNA repair and cell cycle control, but are not directly interacting [24], and the respective protein products do not show any homology [25]. However, it is interesting that breast cancers related to mutations of either BRCA1 or BRCA2 result in tumors with a similar phenotype of high genomic instability [26]. The BRCA1 protein presents its function via its ubiquitin ligase activity, which implicate in DNA repair pathways in response to DNA damage, cell cycle checkpoints, and mitosis by targeting proteins for degradation [27, 28].

BRCA2 acts with BRCA1 and RAD51 in genotoxic stress response [29]. BRCA2 also functions in exit of mitosis and is essential for formation of the contractile ring and appropriate abscission [30]. This function is in accordance with the observed genetic instability in cells lacking BRCA2. Loss of heterozygosity for BRCA1 and BRCA2 is determined in nearly all BRCA1- and BRCA2-associated carcinomas, correspondingly [31]. Hereditary breast cancer, appearing in carriers of mutations in the BRCA1 and BRCA2 genes, differs from sporadic breast cancer and from non-BRCA1/2 familial breast carcinomas, which imply defects in specific pathways [32]. Particularly, BRCA1 carcinomas have the basal-like phenotype and are high-grade, highly proliferating, estrogen receptor-negative, and HER2-negative breast carcinomas, characterized by the expression of basal markers such as basal keratins, P-cadherin, and epidermal growth factor receptor.

Inherited mutations in breast cancer predisposition genes, mainly BRCA1 and BRCA2, account for approximately 5–10 % of breast cancer cases [33]. Most mutations in BRCA1 and BRCA2 result in unstable protein products; however, how this led to cancer predisposition is not obvious, and as yet, no treatment methods have been developed to target BRCA1 functions and mutations [34]. However, it is possible that mutations that are related with increased cancer risk might produce gene products that interfere with tumor suppressor pathways or support oncogenic pathways.

Germ line mutation of BRCA1 increases the risk of having breast cancer. Genetic factors comprise about 5 % of all breast cancer cases. However, somatic BRCA1 mutations are seldom determined in sporadic breast tumors. BRCA1 methylation has been described to take place in sporadic breast tumors and to be accompanied with decreased gene expression. Hence, epigenetic modification and deletion of the BRCA1 gene might act as Knudson’s two “hits” in sporadic breast tumorigenesis [35, 36].

Retrospective studies explored a high level of responsiveness to platin derivatives in BRCA-associated tumors [37] and first clinical trials demonstrate good efficacy and tolerability for PARPs, or poly ADP (adenosine diphosphate)-ribose polymerase inhibitors, in mutation carriers with advanced breast and ovarian cancers [38]. But, the advantages of risk-reducing prophylactic surgery in mutation carriers have been verified [39].

The tumor suppressor gene p53 is located on 17p13.1. P53 somatic change is determined in approximately 50 % of all human cancers [40]. MDM2 can inactivate the p53 through binding to the transactivation domain of p53. High expression level of this gene can cause excessive inactivation of p53 tumor suppressor protein. MDM2 targets p53 for proteasomal degradation through E3 ubiquitin ligase activity. Regulating p53 activity with MDM2 inhibitor is a striking approach for treatment of cancer [41]. A small-molecule MDM2 antagonist, nutlin-3, has been developed at last. Cancer cells with MDM2 gene amplification are most susceptible to nutlin-3 in vitro and in vivo. It is suggested that patients with wild-type p53 tumors may profit from antagonists of the p53-MDM2 interaction [42].

Hypermethylated in cancer 1 (HIC1, also named ZBTB29 or ZNF901) is located at 17p13.3. It is a candidate tumor suppressor gene, which generally undergoes allelic loss in breast and other human cancers. High HIC1 protein expression has been accompanied with better outputs in breast cancers. Lastly, it is demonstrated that HIC1 can hold down the ephrin-A1 transcription and it involves in the pathogenesis of epithelial cancers. Restoration of HIC1 in breast cancer cells causes a growth arrest in vivo [43]. It is shown that HIC1 controls breast cancer cell responses to endocrine therapies. A demethylating drug 5-aza-2′-deoxycytidine can restore the HIC1 expression in MDAMB231 cells. Hence, restoration of HIC1 function by demethylation may suggest a therapeutic opportunity in breast cancer [44].