Breast Cancer

We present the clinical and pathological findings of non-palpable breast cancer presenting an axillary mass in 8 patients at the National Cancer Center Hospital and in 89 cases previously reported in Japan. Mammography and ultrasonography were positive in 26.4% and 26.8% of cases, respectively. 82 (94.3%) of 87 patients underwent mastectomy as a local control. In 19 (30.6%) of 62 patients, the pathological size of the lesion was less than 5 mm. In 15 patients primary tumors could not be identified pathologically. The number of nodes involved ranged from 1–55 with a median of 5. There was no significant correlation between the number of involved nodes and the size of the axillary mass, nor between the number of involved nodes and the pathological size of the primary breast lesion. The 5-year survival rate was 59.4%. There was no statistically significant difference in 5-year survival rates between occult breast cancer and palpable breast cancer in each nodal category. Only the number of involved nodes was a reliable prognostic factor. Unlike palpable breast cancer, the pathological size of the primary tumor was not a predictor of prognosis. In this respect, the biological behavior of occult breast cancer is quite different from that of palpable breast cancer.

Recent studies have indicated that the response to chemotherapy and the prognostic impact of a pathological complete response (pCR) after neoadjuvant chemotherapy differ among breast cancer subtypes. Predictors of response to chemotherapy and prognostic factors for survival might be different in estrogen receptor (ER)-positive breast cancer. Women with Stage II to III ER-positive HER2-negative breast cancer treated with anthracycline and taxane-containing neoadjuvant chemotherapy between 2003 and 2011 were retrospectively analyzed. Expression of forkhead box A1 (FOXA1), B cell lymphoma 2 (BCL2) and microtubule-associated protein tau (MAPT) as well as ER, progesterone receptor, HER2 and Ki67 was examined by immunohistochemistry in pre- and post-treatment specimens. Factors predictive of response to neoadjuvant chemotherapy and distant disease-free survival were analyzed. Tumor grade was positively correlated with Ki67 expression. Expression levels of ER were positively correlated with expression levels of HER2, BCL2, FOXA1 and MAPT in pre-treatment tumors. The Ki67 labeling index was the only factor that was significantly associated with clinical response measured by the reduction of tumor volume and pCR. Lymph node status, expression of ER before neoadjuvant chemotherapy and expression of FOXA1 after neoadjuvant chemotherapy were significantly associated with distant disease-free survival, both by univariate and multivariate analyses. Patients with ER-positive HER2-negative breast cancer should be selected for neoadjuvant chemotherapy. FOXA1 expression could be a prognostic marker in ER-positive breast cancer.

Breast reconstruction is usually performed with autologous tissue or mammary prostheses, and a single method is generally selected for the most reconstruction cases. We combined these two methods of breast reconstruction. In the first stage, a tissue expander was applied to maintain space for the breast, and in the next stage the space was replaced with autologous tissue. This combined method was performed in 7 cases with good results. Some advantages or this method became clear, especially in the case of immediate breast reconstruction: 1) the patient has time to objectively consider breast reconstruction using autologous tissue after the emotional trauma of mastectomy had subsided 2) no additional surgical scar remains on the chest wall 3) the exact site and the exact amount of autologous tissue can be ascertained by measuring the volume of the tissue expander 4) there is no breast-less period, and 5) the patient’s daily life is unaffected. We believe this combined procedure will contribute to a better quality of life for those who experience breast cancer and mastectomy as well as other conventional reconstructive procedures.

Breast cancer is a commonly diagnosed female cancer in the world. Triple-negative breast cancer (TNBC) is the most dangerous and biologically aggressive subtype in breast cancer which has a high mortality, high rates of relapse and poor prognosis, representing approximately 15–20% of breast cancers. TNBC has unique and special biological molecular characteristics and higher immunogenicity than other breast cancer types. On the basis of molecular features, TNBC is divided into different subtypes and gets various treatments. Especially, immunotherapy becomes a promising and effective treatment to TNBC. However, not all of the TNBC patients are sensitive to immunotherapy, the need of selecting the patients suitable for immunotherapy is imperative. In this review, we discussed recent discoveries about the immune-related factors of TNBC, including tumor-infiltrating lymphocytes (TILs), programmed death-ligand protein-1 (PD-L1), immune gene signatures, some other emerging biomarkers for immunotherapy effectivity and promising biomarkers for immunotherapy resistance. In addition, we summarized the features of these biomarkers contributing to predict the prognosis and effect of immunotherapy. We hope we can provide some helps or evidences to clinical immunotherapy and combined treatment for TNBC patients.

A 67-year-old woman with angiosarcoma of the left breast is presented. Physical findings showed a hard mass in the left breast with skin discoloration and erythema. Mammography showed a high density shadow in the mass without microcalcification and spicula. On ultrasonography, a hypoechoic mass with an ill-defined boundary was detected. On MRI, the tumor had low signal intensity on Tl-weighted images, and higher signal intensity on T2-weighted images. MRI with Gd-DTPA images showed higher signal intensity on Tl-weighted images with relatively lower intensity in the central area of the tumor. The artery supplying the tumor derived from the left inner thoracic artery and was visualized on three-dimensional dynamic MRI angiography. Initially misdiagnosed as inflammatory breast cancer, an arterial injection of CPA (100 mg) and 5-FU (500 mg) had been performed preoperatively. The definitive diagnosis of angiosarcoma was established by intraoperative frozen section examination. She underwent modified radical mastectomy and is now free of recurrence. This case emphasizes the difficulties in the clinical diagnosis of angiosarcoma of the breast.

Estrogen (E2) palys critical roles in the development of tumors in female reproductive organs. Development of most breast cancers is dependent on E2 in most cases. Most E2 actions are considered to be exerted through two subtypes of Estrogen receptors (ERs), ER α and ER β. ERs belong to the nuclear receptor superfamily, and act as ligand-inducible transcription factors to activate transcription of a particular set of the target genes. Ligand-bound ER recruits at least two distinct classes of coactivator complexes. In estrogen-dependent breast cancer, growth factors are shown to often act synergisticaly with E2, and the breast cancer often become resistant to treatment of estogen antagonists. However, the molecular basis of this coupled regulation of growth factor- and ER-mediated signaling and hormone-resistance are largely unknown. We have previously shown that MAP (mitogen-activated protein) kinase (MAPK) activated by growth factors phosphorylates and potentiates the N-terminal transactivation function (AF-1), indicating a possible molecular mechanism of a novel cross-talk between two signalings (Katoet al, 1995). Furthermore, we have identified a coactivator that specifically interacts with ER α AF-1 (Endohet al, 1999). In this review, this cross-talk is discussed in terms of the transactivation function of ERs and their coactivators.

Recently, interferon-inducible guanylate binding protein (GBP2) has been discussed as a possible control factor in tumor development, which is controlled by p53, and inhibits NF-Kappa B and Rac protein as well as expression of matrix metalloproteinase 9. However, the potential role that GBP2 plays in tumor development and prognosis has not yet been studied. We analyzed whether GBP2 mRNA levels are associated with metastasis-free interval in 766 patients with node negative breast carcinomas who did not receive systemic chemotherapy. Furthermore, response to anthracycline-based chemotherapy was studied in 768 breast cancer patients. High expression of GBP2 in breast carcinomas was associated with better prognosis in the univariate (P < 0.001, hazard ratio 0.763, 95 % CI 0.650–0.896) as well as in the multivariate Cox analysis (P = 0.008, hazard ratio 0.731, 95 % CI 0.580–0.920) adjusted to the established clinical factors age, pT stage, grading, hormone and ERBB2 receptor status. The association was particularly strong in subgroups with high proliferation and positive estrogen receptor status but did not reach significance in carcinomas with low expression of proliferation associated genes. Besides its prognostic capacity, GBP2 also predicted pathologically complete response to anthracycline-based chemotherapy (P = 0.0037, odds ratio 1.39, 95 % CI 1.11–1.74). Interestingly, GBP2 correlated with a recently established T cell signature, indicating tumor infiltration with T cells (R = 0.607, P < 0.001). GBP2 is associated with better prognosis in fast proliferating tumors and probably represents a marker of an efficient T cell response.

Breast cancer is the most common cause of cancer death among women worldwide, and diet plays an important role in its prevention and progression. Radiotherapy has a limited but important role in the management of nearly every stage of breast cancer. We studied whether equol, the major metabolite of the soybean isoflavone daidzein, could enhance radiosensitivity in two human breast cancer cell lines (T47D and MDA-MB-231). MTT assay was used to examine equol’s effect on cell viability. Sensitivity of cells to equol, radiation and a combination of both was determined by colonogenic assays. Induction of apoptosis by equol, radiation and the combination of both was also determined by acridine orange/ethidium bromide double staining fluorescence microscopy. DNA strand breaks were assessed by Comet assay. MTT assay showed that equol (0.1–350 μM) inhibited MDA-MB-231 and T47D cell growth in a time- and dose-dependent manner. Treatment of cells with equol for 72 h (MDA-MB-231) and 24 h (T47D) was found to inhibit cell growth with IC50 values of 252 μM and 228 μM, respectively. Furthermore, pretreatment of cells with 50 μM equol for 72 h (MDA-MB-231) and 24 h (T47D) sensitized the cells to irradiation. Equol was also found to enhance radiation-induced apoptosis. Comet assay results showed that the radiosensitizing effect of equol was accompanied by increased radiation-induced DNA damages. These results suggest for the first time that equol can be considered as a radiosensitizing agent and its effects may be due to increasing cell death following irradiation, increasing the remaining radiation-induced DNA damage and thus reducing the surviving fraction of irradiated cells.

The clinical usefulness of circulating tumor markers in breast cancer as recurrence indicators during follow-up or monitoring treatment response is still an open question. There are some patients with normal tumor marker levels who have apparent recurrence foci. In this study, we evaluated the relationships between CEA or CA15-3 levels and clinicopathological factors or outcome in patients who had died from recurrent breast cancer. Two hundred-twenty deceased patients who had had recurrent or advanced breast cancer and who had been treated between 1986 and 2000 were enrolled in a retrospective study. Serum CEA and CA15-3 were measured regularly during the clinical course until death. The rates of CEA and CA15-3 positivity were 41.4% and 50.9% at the time of recurrence, and rose to 67.3% and 76.8% after recurrence, respectively. The CA15-3 and CEA positivity rates significantly correlated with ER and PgR status. Serum CA15-3 status correlated significantly with survival after recurrence. Patients with CA15-3 negativity had poorer prognoses than CA15-3 positive patients. Multivariate analysis revealed that CA15-3 status was one of the significant factors for survival after recurrence. Tumor markers, especially CA15-3, might reflect the biological characteristics of tumors such as ER or PgR status, and may be useful prognostic predictors in recurrent breast cancer. Elevated CA15-3 levels correlated with positive estrogen receptor and favorable outcome in deceased patients with recurrent breast cancer.