Breast Cancer

Motivating women with breast cancer to engage in regular physical activity may be an enormous challenge given the common side effects of breast cancer treatment. The objective of this narrative review is to briefly summarize recent research evidence examining the influence of physical activity on commonly occurring side effects of breast cancer treatment. Overall, current research evidence indicates that regular participation in physical activity after breast cancer diagnosis may mitigate common side effects of breast cancer adjuvant therapy, including fatigue, depression, impaired quality of life, decreased muscular strength, decreased aerobic capacity, and weight gain. Future research could examine the influence that physical activity has on the effectiveness of breast cancer treatment. Implications for health care professionals are discussed.

Presently, hormonal therapy targeting estrogen receptors is the most effective treatment available for luminal breast cancer. However, many patients relapse after the therapy. It has been suggested that cancer stem-like cells are involved with hormonal therapy resistance; in the present study, we evaluated this hypothesis. In the present study, we used our previously established hormonal therapy-resistant cell lines, including aromatase inhibitor (AI)-resistant cells (Type 1 and Type 2) and fulvestrant-resistant cells (MFR). AI-resistant cell lines expressing ER (Type 1 V1 and V2) showed high cancer stemness in terms of their CD44/CD24 expression and side populations, which were stimulated by the addition of estrogen and inhibited by fulvestrant. However, ALDH activity was lower than in the ER-negative resistant cells, suggesting that the stemness of luminal cells is distinct from that of basal-like breast cancer cells. The migration and invasion activity of the ER-positive Type 1 V1 and V2 cells were higher than in the ER-negative cell lines, Type 2 and MFR. Fractionation of parental cells based on CD44/CD24 expression and colony formation assay indicated that CD44+/CD24+ cells might be the origin of hormonal therapy-resistant cells. This population reconstituted various other subpopulations under estrogen deprivation. These results indicate that hormonal therapy resistance is closely related to the cancer stem cell-like properties of luminal breast cancer.

Akt is a serine/threonine kinase that has been demonstrated to play an important role in survival when cells are exposed to different apoptotic stimuli. Recent studies show that aberrant activation of Akt in breast carcinoma is associated with a poor prognosis and resistance to endocrine therapy and chemotherapy. The Akt signaling pathway is currently attracting considerable attention as a new target for effective therapeutic strategies. We investigated the incidence of Akt activation in 252 primary breast carcinomas and relationships among the activation of Akt, HER2 overexpression, hormone receptor expression, and alteration of the PTEN gene. Eighty-four cases (33.3 %) were positive for pAkt expression. pAkt was significantly associated with HER2 overexpression (p<0.0001) and LOH at the PTEN gene locus (p<0.01). There was an inverse correlation between pAkt and PR (p<0.05). We also retrospectively examined the relationship between Akt activation and the efficacy of endocrine therapy for metastatic breast cancer. Of these 36 metastatic breast cancer cases, 12 cases (33.4%) were considered to show positive pAkt expression. In the pAkt-positive patients, endocrine therapy demonstrated worse efficacy than in pAkt-negative patients (p<0.01). In addition, the clinical benefit was the smallest in the patients positive both for HER2 and pAkt (p<0.01). The clinical benefit rate of estrogen deprivation therapy with AI or LHRH agonist was significantly lower in the pAkt-positive patients than that in the pAkt-negative ones (p<0.05), and there was a tendency for the clinical benefit of SERM to be smaller in the pAkt-positive patients (p=0.09). These findings therefore suggest that Akt activation induces endocrine resistance in metastatic breast cancer, irrespective of the kind of endocrine agents that were administered. Our findings indicate that the activation of Akt in the downstream pathway of HER2 plays an important role in resistance to endocrine therapy for breast cancer. Our findings suggest that pAkt may be a useful predictor of resistance to endocrine therapy for breast cancer, while also suggesting that the inhibition of Akt may increase the efficacy of endocrine therapy.

A rare case of intracystic papillary carcinoma (IPC) with invasion had synchronous metastases to the liver at presentation. A 57-year-old postmenopausal woman noticed a right breast tumor 7 months prior to admission. Mammography showed an oval mass measuring 3.1 cm in diameter with no calcification, and ultrasonography showed an intracystic tumor with a papillary growth pattern. Fine-needle aspiration cytology revealed adenocarcinoma. Excisional biopsy revealed intracystic solid papillary carcinoma with invasion. The tumor was a clear-cell type with extracellular mucin. Two months after the initial biopsy, a screening ultrasonographic examination of the liver showed multiple hyperechoic masses. Abdominal contrast-enhanced CT scan and magnetic resonance imaging (MRI) showed multiple hypervascular masses compatible with metastatic tumors. No suspicious lesions were detected on examinations for malignancy in other organs. Distant metastases in cases of IPC with invasion are very rare. The potential of distant metastasis in IPC with invasion and the difficulty of evaluating invasive foci should be recognized. Careful evaluation of distant metastases is recommended.

The mechanism by which pregnancy impacts breast cancer risk remains poorly understood. There is a need for detailed quantification of risk in nulliparous women. We therefore have undertaken a case-referent study of breast cancer employing data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan, examining the impact of reproductive and anthropometric factors on breast cancer risk among nulligravid women compared with their parous counterparts. In total, 2,032 breast cancer cases were included, and 17,848 women, confirmed as free of cancer, were recruited as a reference group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple logistic regression analysis. A protective effect of later age at menarche was observed among parous women, but it did not alter risk in nulligravid cases. The risk increment with a family history appeared to be most pronounced among premenopausal cases with no history of pregnancy (OR=2.68, 95% CI: 1.41-5.11). Among postmenopausal women, positive associations with height and current body mass index (BMI) in the nulligravid group were similar to those observed in the parous group. The present study indicated that age at menopause, family history in premenopausal women, and height and obesity in postmenopausal women seemed to exert more influence in nulligravid women. Formal tests for interaction between maternity status and these factors, however, did not prove statistically significant. Our findings suggest that established risk factors for breast cancer have an additive impact with nulligravid status. Thus, it is implied that obesity control for all women, including nulliparous individuals, is important from a practical viewpoint for primary breast cancer prevention.

Perioperative dose-dense chemotherapy (DDCT) with granulocyte-colony stimulating factor (G-CSF) prophylaxis is a standard treatment for patients with high-risk breast cancer. The approval of this approach in Japan led to the widespread adoption of DDCT, despite limited efficacy and safety data among Japanese patients. We evaluated the efficacy and safety of neoadjuvant DDCT for Japanese patients with breast cancer. This prospective, multicenter, phase II study evaluated 52 women with operable human epidermal growth factor receptor 2-negative breast cancer and axillary lymph node metastasis. Neoadjuvant DDCT (adriamycin plus cyclophosphamide or epirubicin plus cyclophosphamide followed by paclitaxel) was administrated every 2 weeks with G-CSF support. The study endpoints were the rates of pathological complete response (pCR), febrile neutropenia, treatment completion, toxicities, and the relative dose intensity (RDI). The pCR rate was 21.9% (9/41) and the triple-negative (TN) subtype was significantly associated with a high pCR rate (triple-negative: 53.3% vs. luminal A: 7.7% and luminal B: 0%; p = 0.003). The treatment completion rate was 80.8% (42/52) and the average RDI was 98.9%. Most adverse events were manageable and tolerable. Six patients (11.5%) developed febrile neutropenia. Grade 3–4 adverse events were slightly more common among older patients (57%) with a low protocol completion rate (≥ 65 years: 42.9% vs. <65 years: 86.7%, p = 0.0062). The pCR rate for DDCT was similar to that of standard chemotherapy, although it was remarkably effective for the TN subtype. DDCT may be feasible for Japanese patients with breast cancer although caution is needed for older patients.

Assessment of pectoralis muscle invasion is important for treatment planning for breast cancer. We evaluated the usefulness of breast magnetic resonance (MR) imaging for the detection of tumor invasion of the pectoralis muscle in breast cancer patients. Materials and Method: A total of 306 breast MR examinations were performed preoperatively. Three-dimensional gradient echo sequences, at a section thickness of 1.5 or 2 mm were obtained with administration of gadolinium-DTPA. All patients underwent surgery. In 33 breasts, disruption of the fat plane between tumor and muscle was noted. Seven of 33 cases showed muscle enhancement contiguous to enhanced tumors. Pathology reports indicated that 5 of 7 of the tumors involved muscle invasion. Of the 2 false positive cases, one showed muscle enhancement because of a previous biopsy, and the other was incorrectly interpreted as showing muscle enhancement. Of the 26 breasts which did not demonstrate muscle enhancement, none were found at surgery to have tumor involvement. Enhancement of the pectoralis muscle correlates well with muscle invasion, but there are a few potential pitfalls. Disruption of the fat plane between tumor and muscle, without muscle enhancement, might not indicate tumor involvement of the pectoralis muscle.

Triple-negative breast cancer is characterized as a cancer with a high malignancy potential and a poor prognosis. Therefore, early detection of this subtype of breast cancer is vital. In this paper, we describe the mammography and ultrasound findings of triple-negative breast cancer in a large population and investigate the specific features of this subtype. From January 2007 to April 2010, mammography and ultrasound findings of 88 patients with triple-negative breast cancer were retrospectively reviewed. In this cohort, 52 patients underwent neoadjuvant chemotherapy. We compared the pathological chemotherapy effects and radiological findings among these patients. Mammograms were reviewed according to the Japanese mammography guideline. Ultrasound findings were classified as masses, low echoic area, distortions, and calcifications. Noted features included shapes, patterns of internal echoes, posterior echoes, vascularity, and elasticity scores. On mammography, triple-negative breast cancers frequently presented with a mass (62.4%). Masses with microlobulated margins were the most frequent (39.6%), indistinct (32.0%) and circumscribed (20.8%) were commonly observed, but spiculated margins were rare (4.7%). On ultrasound, cancers were more likely to present as a mass (92.5%), and less likely to show attenuating posterior echoes (8.8%). Of the 40 cases obtained via elasticity imaging, 35 (87.5%) lesions were scored as 4 or 5. There were no significant differences in the mammography or ultrasound findings between the chemotherapy effects. Mammography and ultrasound imaging together revealed that the morphological features of triple-negative breast cancer include a lobulated mass, with less attenuating posterior echoes, some vascularity, and low elasticity.