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A lumpectomy followed by radiation treatment may be just as effective in treating breast cancer as a mastectomy. A lumpectomy is a method of removing the tumor while preserving most of the breast. Of 237 women with breast cancer followed by the National Cancer Institute, 116 had received a mastectomy and 121 had a lumpectomy plus radiation. Ten-year survival rates were 77% in the lumpectomy group and 75% in the mastectomy group. Seventy-two percent of the women in the lumpectomy group were in remission at 10 years, compared to 69% of those in the mastectomy group. Eighteen patients in the lumpectomy group had a recurrence of cancer in the breast and were successfully treated with a mastectomy. Fifteen were disease-free three months to 10 years after the mastectomy. In both groups, women with smaller tumors and no spread of cancer to the lymph nodes had better survival rates.

Purpose: Atypical ductal and atypical lobular hyperplasia (AH) of the breast are important proliferative lesions which are associated with a significantly increased risk for breast cancer. The breast cancer which develops in association with AH may occur synchronously, representing local progression, or metachronously at a later date in either the ipsilateral or contralateral breast. These high-risk characteristics of AH suggest they contain significant genomic changes.Methods: To define the genomic changes in AH, a comprehensive review of the literature was conducted to identify the numerical chromosomal and structural chromosomal changes, DNA methylation, and gene expression abnormalities in atypical ductal and atypical lobular hyperplasia.Results: AHs are characterized by advanced genomic changes including aneuploidy, loss of heterozygosity, gross chromosomal rearrangements such as amplifications and large-scale deletions, DNA methylation of tumor suppressor and other genes, and gene expression differences between AH and surrounding normal breast tissue including significant estrogen receptor expression. Many of these changes are shared by an associated synchronous breast cancer, consistent with an important precursor role for AH. At the same time, many of the genomic changes of AHs are also shared by common sporadic breast cancer, consistent with a high risk for future development of metachronous breast cancer.Conclusions: This molecular profile should help clarify the genomic characteristics and malignant predisposition of AH, and aid in the identification of new targets for the prevention of breast cancer [ABSTRACT FROM AUTHOR]

BACKGROUND: There is a strong need to define the molecular changes in normal at-risk breast epithelium to identify biomarkers and new targets for breast cancer prevention and to develop a molecular signature for risk assessment. Improved methods of breast epithelial sampling are needed to promote whole-genome molecular profiling, increase ductal epithelial cell yield, and reduce sample cell heterogeneity. METHODS: We developed an improved method of breast ductal sampling with ductal lavage through a 22-gauge catheter and collection of ductal samples with a microaspirator. Women at normal risk or increased risk for breast cancer were studied. Ductal epithelial samples were analyzed for cytopathologic changes, cellular yield, epithelial cell purity, quality and quantity of DNA and RNA, and use in multiple downstream molecular applications. RESULTS: We studied 50 subjects, including 40 subjects at normal risk for breast cancer and 37 subjects with non-nipple aspirate fluid-yielding ducts. This method provided multiple 1.0 mL samples of high ductal epithelial cell content (median ≥8 samples per subject of ≥5,000 cells per sample) with 80%-100% epithelial cell purity. Extraction of a single intact ductal sample (fluid and cells) or the separate frozen cellular component provided DNA and RNA for multiple downstream studies, including quantitative reverse transcription- polymerase chain reaction (PCR) for microRNA, quantitative PCR for the human telomerase reverse transcriptase gene, whole-genome DNA amplification, and array comparative genomic hybridization analysis. CONCLUSION: An improved breast epithelial sampling method has been developed, which should significantly expand the acquisition and biomarker analysis of breast ductal epithelium in women at risk for breast cancer. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) in body fluids are candidate diagnostics for a variety of conditions and diseases, including breast cancer. One premise for using extracellular miRNAs to diagnose disease is the notion that the abundance of the miRNAs in body fluids reflects their abundance in the abnormal cells causing the disease. As a result, the search for such diagnostics in body fluids has focused on miRNAs that are abundant in the cells of origin. Here we report that released miRNAs do not necessarily reflect the abundance of miRNA in the cell of origin. We find that release of miRNAs from cells into blood, milk and ductal fluids is selective and that the selection of released miRNAs may correlate with malignancy. In particular, the bulk of miR-451 and miR-1246 produced by malignant mammary epithelial cells was released, but the majority of these miRNAs produced by non-malignant mammary epithelial cells was retained. Our findings suggest the existence of a cellular selection mechanism for miRNA release and indicate that the extracellular and cellular miRNA profiles differ. This selective release of miRNAs is an important consideration for the identification of circulating miRNAs as biomarkers of disease. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of an ipsilateral breast tumor recurrence (IBTR) after breast-conservation therapy (BCT) on survival. Methods and Materials: One hundred twenty-one women were randomized to BCT. Patients with an IBTR were analyzed to determine survival. Analysis was performed with Kaplan-Meier estimates, log-rank tests, and time-dependent covariate Cox models. Results: At a median follow-up of 18.4 years, 27 patients had an IBTR. The median survival time after IBTR was 13.1 years. The 5-year survival rate was 91.8% (95% confidence interval [CI], 81.5–100%). The 10-year survival rate was 54.3% (95% CI, 35.8–82.6%). According to a Cox model with time-dependent covariates, the hazard ratio or relative risk of dying for those with an IBTR at <5.3 years after BCT relative to patients without an IBTR after BCT is 1.47 (95% CI, 1.02–2.12%; p = 0.04). The hazard ratio for those who relapse after 5.3 years is 0.59 (95% CI, 0.22–1.61%; p = 0.31). Age at randomization, original tumor size, and the presence of positive regional nodes at initial presentation were not found to be associated with decreased survival. Conclusions: There seems to be a significant association of early IBTR after BCT with decreased survival. Local control should be maximized. [Copyright &y& Elsevier]

Background: Preoperative chemotherapy for stage II breast cancer may reduce locoregional tumors and provides initial treatment for systemic micrometastases. We conducted a prospective, randomized trial to evaluate the ability of intensive preoperative chemotherapy to enhance the outcome of this approach. Methods: Patients with clinical stage II breast cancer (T2N0, T1N1, and T2N1) were prospectively randomized to receive either preoperative or postoperative chemotherapy with five 21-day cycles of fluorouracil, leucovorin calcium, doxorubicin, and cyclophosphamide (FLAC)/granulocyte-colony-stimulating factor. Local therapy consisted of modified radical mastectomy or segmentectomy/axillary dissection/breast radiotherapy, according to patient preference. Results: Fifty-three women were randomized (26 preoperative chemotherapy and 27 postoperative chemotherapy). The objective clinical response rate of the primary tumor to preoperative chemotherapy was 80%, and the pathologic complete response rate was 20%. Preoperative chemotherapy reduced the overall incidence and number of axillary lymph node metastases. There was no difference in the use of breast-conserving local therapy between the two treatment arms. There were 20 local/regional or distant recurrences (9 preoperative and 11 postoperative). There was no difference in the overall or disease-free survival between the preoperative and postoperative chemotherapy arms. Conclusions: Preoperative FLAC/granulocyte-colony-stimulating factor chemotherapy was effective against local/regional tumors in stage II breast cancer but was otherwise comparable to postoperative chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose. In women with breast cancer, knowledge of the local/regional extent of the tumor is essential for staging, treatment planning, monitoring response to therapy, and follow-up. Positron emission tomography (PET) is an important imaging test which can detect tumor at multiple sites in women with breast cancer. We compared the ability of PET to provide a comprehensive view of the local/regional extent of tumor in women with stage I, II and stage III, IV breast cancer. Materials and methods. Forty-six women with breast cancer underwent PET using 18F-FDG. 18FDG uptake in the breast primary tumor, associated skin, axillary and internal mammary lymph nodes, and the contralateral breast was determined qualitatively, and correlated with histologic, clinical and radiographic findings. Results. Twenty-four patients were premenopausal and 22 were postmenopausal, with the following distribution according to clinical stage: stage I – 2 patients, stage II – 16, stage III – 16, stage IV – 12 patients. Among stage I, II patients, the sensitivity for detection of the primary tumor was 83.3%, and for detection of axillary lymph node metastases was 42.9%. 18FDG-PET was negative for the breast skin, contralateral breast, and internal mammary lymph nodes in all stage I, II patients, in agreement with clinical and radiographic findings. Among 28 stage III, IV patients, the sensitivity of 18FDG-PET for detection of the primary tumor was 90.5%, and for detection of axillary lymph node metastases 83.3%. Fourteen patients had clinically advanced changes in the skin, and the sensitivity of PET for detection of skin changes was 76.9%. 18FDG-PET was positive in the internal mammary lymph nodes in 25.0%, and negative in the contralateral breast in all patients with stage III, IV breast cancer. 18FDG-PET was studied in 10 patients following neoadjuvant chemotherapy, and showed a strong correlation with clinical response, and with clinical and pathological findings post-treatment at multiple local/regional sites. Conclusion.18FDG-PET can provide a comprehensive image of local/regional tumor in women with breast cancer. 18FDG-PET may play a greater role in women with stage III, IV breast cancer because of increased sensitivity and the increased involvement of multiple local/regional sites with tumor. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic inflammation is an important cause of multiple cancers. While chronic inflammation is present in breast cancer and may influence its outcome, its role in the initiation and development of breast cancer is unclear. A review of the literature was conducted to determine if chronic inflammatory processes are present, both systemically and in normal breast tissue, which may contribute to the development of breast cancer in women. This indicates that several chronic inflammatory factors may influence breast cancer development, with some such as adipose tissue and obesity occurring early in breast carcinogenesis, while others, such as the microbiome and inflammation from genomic changes, may occur with the transition to malignancy. Chronic inflammation appears to be an important risk factor for breast cancer and may influence both the development and conduct of breast cancer. Chronic inflammation contributes to the malignant transformation of several malignancies and is an important component of breast cancer. The role of chronic inflammation in the initiation and development of breast cancer from normal breast tissue, however, is unclear and needs to be clarified. A review of the literature was conducted to define the chronic inflammatory processes in normal breast tissue at risk for breast cancer and in breast cancer, including the role of lymphocyte and macrophage infiltrates, chronic active adipocytes and fibroblasts, and processes that may promote chronic inflammation including the microbiome and factors related to genomic abnormalities and cellular injury. The findings indicate that in healthy normal breast tissue there is systemic evidence to suggest inflammatory changes are present and associated with breast cancer risk, and adipocytes and crown-like structures in normal breast tissue may be associated with chronic inflammatory changes. The microbiome, genomic abnormalities, and cellular changes are present in healthy normal breast tissue, with the potential to elicit inflammatory changes, while infiltrating lymphocytes are uncommon in these tissues. Chronic inflammatory changes occur prominently in breast cancer tissues, with important contributions from tumor-infiltrating lymphocytes and tumor-associated macrophages, cancer-associated adipocytes and crown-like structures, and cancer-associated fibroblasts, while the microbiome and DNA damage may serve to promote inflammatory events. Together, these findings suggest that chronic inflammation may play a role in influencing the initiation, development and conduct of breast cancer, although several chronic inflammatory processes in breast tissue may occur later in breast carcinogenesis. [ABSTRACT FROM AUTHOR]