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Multiple studies have shown that women with mammographically dense breasts are at a higher risk of developing breast cancer and that the upper outer quadrant of the breast is the most frequent site where breast cancer is located. There is no association, according to findings of a study published in BMC Cancer. However, the study did reconfirm that breast cancer was most likely to occur in the upper outer quadrant of the breast in a patient cohort of 110 women. Research to investigate the relationship between quadrant density and tumors occurring in a specific quadrant location has been limited by lack of a reliable method to measure quantitative density on mammography as well as by lack of a standardized method to divide a breast into four well-defined quadrants. A multinational research team from the Department of Radiological Sciences at the University of California in Irvine and hospitals in Taiwan developed a computer algorithm-based segmentation method to quantitively analyze breast density. They used this with an established method to divide a breast into four quadrants based on craniocaudal and mediolateral oblique mammography using the nipple and the chest wall as references. Co-author Min-Ying Su, PhD, a professor of radiology and director of the Center for Functional Onco-Imaging at the University of California, and co-researchers retrospectively reviewed the mammography results of 213 women with pathologically confirmed breast cancer who had not previously had breast cancer. A total of 110 women who had breast cancer located in only one quadrant comprised the patient cohort for evaluation. These patients were separated into four groups based on tumor location. The cancers were identified as invasive ductal (70%), invasive lobular (0.45%), other types of invasive mammary cancer (10%) and ductal carcinoma in situ (15%). The upper outer quadrant had the highest breast area and the highest dense area, with a 20% density. The lower outer quadrant had the majority of cancer (60.9%), followed by the lower inner quadrant (18.2), the upper inner quadrant (14.5%), and the lower outer quadrant (6.4%). The upper outer quadrant had the highest breast and density areas, with a 20% density. The order of breast area and also density area was (in descending order): upper outer quadrant, upper inner quadrant, lower outer quadrant, and lower inner quadrant. The percent density, calculated as the ratio of density area/breast area, in descending order for the other quadrants was: lower outer quadrant (22.8%), lower inner quadrant (20.5%) and upper inner quadrant (18.5%). The researchers reported that based on their statistical analysis, comparative results showed that there was no trend, and that the percent density was not associated with tumor occurrence. Differences in quadrant density, described in detail in the article, was attributed mainly to the breast division method, and was not related to the cancer occurrence. REFERENCE
Breast Cancer is one of the most common and well-known cancers diagnosed in the United States. It can occur in both women and men, but is substantially more common in women. With increased awareness and support for breast cancer research, there have been many new advances to how breast cancer is treated. At the Margie Petersen Breast Center, we strive to bring you the most innovative care for your breast cancer and, overall breast health needs.
Determining your type of breast cancer begins with a histological workup, a summary prepared by the pathologist after you undergo a biopsy. Essentially, the histological evaluation is the microscopic analysis of the chemical and cellular properties associated with a suspicious breast tumor. The pathologists here at Providence Saint John’s will also confirm the size of the breast tumor where necessary for breast cancer staging purposes. The histological evaluation is essential to determine the most effective treatment recommendations following surgery.
Your Providence Saint Johns’ pathologist will be able to tell the type of breast cancer and if it is still confined to the breast ducts (DCIS); or whether it has reached infiltrative or invasive status. The pathologist will also be able to determine whether or not the cancer has metastasized to the lymph nodes in the axilla, based on an additional sample from that region. The stage of your cancer is largely a function of the invasive or non-invasive status of the breast cancer, the size of the invasive component, and whether the cancer has spread to the lymph nodes or distant organs. The grade of the breast cancer is related more to the actual microscopic character of the cells in the breast tumor. Based on a variety of cellular features, the histological analysis helps determine the type of breast cancer as well as the grade. Histological classification of breast cancer, into essentially grades 1, 2, and 3, determines the aggressiveness of treatment because higher grades tend to correspond to poorer survival rates and prognosis. What the pathologist will be considering is the degree of tubule formation within the tumor, meaning the number and differentiation of tubules; the mitotic count, or the rate and number of cell divisions; and nuclear pleomorphism which is basically the appearance of the cells and cell nuclei, in increasing amounts of variation and bizarre randomness. A combined score from the three observations determines the histological grade of the breast cancer. The pathologist may also note the presence and amount of necrosis, cell and tissue death and decay, and calcifications. Necrosis tends to be another indicator of an aggressive breast cancer. The use of steroid receptors (estrogen and progesterone) to predict breast cancer outcome and responsiveness to therapy has been used for many years now. In fact, the usual method for measuring the presence of steroid receptors in breast cancer tumors is by immunohistochemistry. There are no hard-and-fast rules for how to interpret the presence of various hormone and hormone receptor levels, but certain generally tendencies can be observed. The most important hormonal indicators to identify are the positive presence of estrogen and progesterone receptors. Breast cancers that over-express high amounts of estrogen and progesterone receptors are likely to be more responsive to endocrine therapy treatment. Estrogen and progesterone receptors levels are detected in the nucleus of normal breast cells and many malignant cancer cells have retained the ability to express hormone receptors as well. Human epidermal growth factor receptor 2 (or HER2, or Her-2/neu/c-erb B2) has been an important aspect of breast cancer histology since about 1987. It has been shown that high levels of either HER2 gene amplification or protein expression tends to result in a poorer breast cancer prognosis. A monoclonal antibody therapy called Trastuzumab was developed to counter the effects of HER2, and its use has been shown to reduce rates of recurrence and mortality in HER2 positive early stage breast cancers. Additional targeted agents against Her2 (like Pertuzamab) have been used more recently in combination with Trastuzumab to achieve greater results. The epidermal growth factor receptor (EGFR or HER1) is a type 1 tyrosine kinase receptor that is expressed in normal breast tissue. Generally speaking, for this receptor to be present higher than expected levels of EGFR are accompanied by low levels of estrogen receptors, and other poor prognostic features. EGFR tends to be associated with grade III breast tumors. This is a gene mutation in a gene important for controlling cell growth and death. For women who have breast cancer, this gene mutation can lead to a significantly increased risk of death. p53 is most commonly associated with tumors in premenopausal women. However, when it occurs in postmenopausal women, it was most commonly associated with a high body mass index. B-cell lymphoma 2 (BCL2) is an antiapoptotic protein. Its presence can be an independent indicator of a favorable prognosis for early-stage breast cancer. One of the newer classifications of breast cancers is based on genes expressed in the tumor. Luminal A and Luminal B are usually hormone receptor positive. Luminal A breast cancers usually have an excellent outcome. Her2neu breast cancers express the Her2neu gene. Basal breast cancers are the most aggressive molecular sub-type and are usually hormone and Her2neu receptor-negative. They can also be triple negative cancers. Some breast tumors may express high levels of proteins that are not normally associated with epithelial cells, like the duct-lining cells most commonly associated with breast cancer, but are derived from basal or myoepithelial cells. There are a number of proteins associated with basal and myoepithelial gene expression, including cytokeratins 5 and 6, and 14, P-cadherin, and p63. Most of these tumors also have a corresponding low expression of ER, PgR, and HER2, and are considered to have a higher risk of metastasis. An antigen called Ki-67 is expressed in the nucleus of neoplastic cells in all phases of a cell cycle, and is therefore thought to be a useful marker for high levels of proliferation. Notable changes in Ki-67 expression following a neoadjuvant treatment by endocrine or hormone therapy have been shown to be a useful predictor of long term outcome in some cases. If we can inhibit new cell growth, Ki-67 levels will also decrease, which tends to predict a good response to chemotherapy. Other proliferation markers in use include p21, p27, cyclin E, and cyclin D1. However, it is still the presence of estrogen and progesterone receptors and Her2 that remain the most useful markers for determining the management of breast cancer. Epidermal growth factor receptors, Ki-67, and Topoisomerase II alpha have high potential as prognostic markers of breast cancer, while other markers such as P53, cyclin E, cyclin D1, p21, p27, Bcl2, bax, bcl-x, and survivin are still in an experimental phase, with limited clinical applicability. In the future, microarray-based high-throughput technologies might be employed to look more closely at the molecular characteristics of breast cancers. Certain genetic/molecular features have been associated with an increased proclivity to metastasize. Certainly, the more we know about your tumor, the more aggressively we can treat it, and it is possible that in the near future these genetic and molecular features of a breast tumor might be included in the determination of histological breast cancer grade. Several of the physicians and surgeons at the Margie Petersen Breast Center at Providence Saint John’s Health Center are also on faculty at the Saint John’s Cancer Institute, and academically renowned research institute. |