Springer Science and Business Media LLC

Several pathologic classification systems have been developed to evaluate tumor response after neoadjuvant chemotherapy (NAC) for breast cancer. We aimed to compare pathologic classification systems and to investigate prognostic factors and risk stratification according to molecular subtype in relation to survival. We retrospectively evaluated pathologic response after NAC in 485 breast cancer patients by applying the National Surgical Adjuvant Breast and Bowel Project B18 trial (NSABP-B18), Miller and Payne system, Chevallier’s classification, Sataloff’s classification, residual cancer burden (RCB), residual disease in breast and nodes (RDBN), and clinical–pathologic stage + estrogen receptor status and grade staging system (CPS + EG). All seven classification systems were significantly associated with overall survival (OS) and distant disease-free survival (DDFS). Regarding intrinsic subtypes, all systems were significantly associated with OS and DDFS for triple-negative tumors. Only RCB had prognostic significance for all four subtypes in relation to both OS and DDFS, and RDBN in DDFS only for all subtypes. In risk factor analyses, lymphovascular invasion (LVI), as well as other classic pathologic prognostic factors such as tumor size, lymph node status, and hormonal receptor status, was significantly associated with both OS and DDFS for the entire study group. Regarding subtypes, LVI was associated with DDFS for each subtype except Luminal B-like tumors. Our results suggest that pathologic classification systems that evaluate residual tumors in both breast and lymph nodes after NAC show better association with clinical outcome. Furthermore, combining LVI with other classic prognostic factors might have prognostic value for the assessment of treatment response after NAC.

Multiple factors which increase a woman's breast cancer risk have been identified. These range from conditions such as lobular carcinomain situ which increase risk to relatively high levels, to reproductive factors such as nulliparity which are associated with only a small increase in risk. When determining an individual's risk, all her potential breast cancer risk factors must be considered. In order for risk information to be meaningful to a woman, risk must be expressed as absolute risk over a defined time interval since there is no uniform agreement on what risk level is high enough to require intervention. At present, careful follow-up or prophylactic mastectomy are the management options available for the woman at increased risk. The efficacy of follow-up including breast self exam, physician exams, and screening mammography for early detection of cancer in a high risk population is unknown. Prophylactic mastectomy, while highly effective, does not provide complete protection from breast cancer and is more radical than the surgery done for established cancer in many cases. Which of these options is chosen by an individual woman is dependent on how much risk she is willing to assume.

The metastasis of cancer to bone is a frequent outcome of common malignancies and is often associated with significant morbidity due to osteolysis. Bone metastasis is also selective in that a disproportionately small number of malignancies account for the majority of tumors which spread to bone. While the mechanisms of bone destruction have been studied, those responsible for the site-specific nature of bone metastasis are poorly understood. As a metastatic target, bone is unique in that it is continuously being remodelled under the influence of local and systemic growth factors, many of which are embedded in the bone matrix. This review summarizes evidence for the hypothesis that the formation of metastatic tumors in bone is the consequence of a unique microenvironment where metastatic cells can alter the metabolism of bone, thereby regulating the release of soluble bone-derived growth factors as a consequence of bone resorption. These, in turn, can modulate the malignant phenotypic properties of receptive cells. Transforming growth factor-β is one factor which can promote the growth and motility of Walker 256 cells, a rat cell line with a propensity to metastasize spontaneously to bone.

The pp32 gene family consists of at least three closely related members, pp32, pp32r1 and pp32r2. In spite of a high degree of identity at the nucleotide level, pp32 functionally behaves as a tumor suppressor where as pp32r1 and pp32r2 are pro-oncogenic. The purpose of this pilot study was to determine pp32-related expression and whether alternative gene use among the pp32 family members occurred in human breast cancer. As a first step, in situ hybridization with a riboprobe capable of hybridizing with all the three members showed abundant pp32-related mRNA in benign ducts and acini and in infiltrating ductal carcinomas. A total of 100/102 cases were positive. Further, a detailed molecular analysis by RT-PCR, cloning, and sequencing was performed in five frozen infiltrating breast carcinomas and matched benign breast tissues. Oncogenic pp32r1 (5/5) and pp32r2 (3/5) expression was observed in carcinomas where as benign breast tissues expressed pp32. 4/5 carcinomas continued to express pp32 but one was devoid of pp32 expression. These results suggest that alternative expression of pp32 family members may be common in human breast cancer and the analysis of the profile of pp32-related expression might be helpful in understanding the role of these genes in breast cancer pathogenesis.

One of the hallmarks of cancer cells is the demand of supply for the synthesis of new membranes involved in cell proliferation and lipids have an important role in cellular structure, signaling pathways and progression of cancer. In this sense, lipid studies have become an essential tool allowing the establishment of signatures associated with breast cancer (BC). In this regard, some metabolic processes including proteins, nucleic acids and lipid synthesis are enhanced as part of cancer-associated metabolic reprogramming, as a requirement for cell growth and proliferation. Pairwise samples of breast active carcinoma (BAC) and breast cancer-free tissues were collected from n = 28 patients and analyzed by MALDI-TOF MS. Major lipid species are identified in the MALDI-TOF mass spectra, with certain phosphatidylinositols (PIs) detectable only in BAC. Statistical analysis revealed significant differences (p < 0.05) between ratios lysophosphatidylcholine (LPC) 16:0/phosphatidylcholine (PC) 16:0_18:2 between AC and CF groups as well as for BC stages II and III. The ratio PC 16:0_18:2/PC16:0_18:1 was statistically different between AC and CF groups. The one-way ANOVA revealed that there are no statistical differences among BC stages (I, II and III) within AC group. Comparing BC stages, the significance impact increased (p < 0.05) with stage. The obtained data revealed MALDI-TOF MS as a powerful tool to explore lipid signatures and the enzyme activity associated with BC and possibly establish novel disease markers.