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We also performed exploratory analyses to investigate treatment effects on sites of first recurrence. After a protocol amendment was approved before the first interim analysis in 2008, we added another secondary end point: invasive-disease–free survival, which was defined according to the Standardized Definitions for Efficacy and End Points in Adjuvant Breast Cancer Trials (STEEP) guidelines. The date of recurrence was defined as the date on which relapse was first suspected, rather than the date on which it was confirmed, to reduce the risk of ascertainment bias. On-site and telephone-based monitoring was performed to ensure that recurrence dates were backdated to the date on which the event was first suspected, when this date preceded clinical, histologic, or imaging confirmation. Viagra Australia website

Study Oversight

The study was sponsored by the University of Sheffield and approved as a United Kingdom national trial by the Clinical Trials Advisory Awards Committee. Grant support was provided by Novartis Pharmaceuticals and was supplemented in the United Kingdom by the infrastructure of the National Cancer Research Network. Novartis Pharmaceuticals donated study supplies of zoledronic acid. The authors developed the study concept, wrote the protocol, and performed and reviewed all analyses. The study was conducted in accordance with the protocol, with amendments to reduce the risk of osteonecrosis of the jaw and to inform both patients and dental practitioners of this risk. The first author wrote the first draft of the manuscript, and all authors were involved in revision and approval of the manuscript. Novartis Pharmaceuticals was given an opportunity to comment on the manuscript, but all decisions on submission of the manuscript for publication were made by the authors and the trial steering committee.

Statistical Analysis

A final analysis was planned after the primary end point (disease-free survival) had occurred in 940 patients, on the basis of the recruitment of 3300 patients during a 3-year period, an anticipated rate of disease-free survival of 75% at 3 years, and a 5% annual rate of loss to follow-up. It was estimated that these numbers would provide a power of 80% to detect a relative reduction of 17% in the rate of disease recurrence or death among patients receiving zoledronic acid, at a two-sided level of significance of 0.05, which would approximate an absolute benefit of 3.7 percentage points.

A single interim analysis was planned after the primary end point had been reached in 470 patients, with a two-sided alpha level of 0.005. After this analysis was performed, on the advice of the independent data and safety monitoring committee, no efficacy data were released. Because the rate of events contributing to the primary end point was lower than predicted (resulting in a combined rate of disease-free survival of 85% at 3 years), an independent statistician who was unaware of the findings and was not involved in the first interim analysis provided revised stopping boundaries for both efficacy and lack of benefit that would allow timely release of a clinically important result. A second interim analysis was planned after the primary end point had occurred in at least 705 patients, along with a 0.5% probability of declaring false positive results (one-sided) or a 5.0% probability of declaring negative results with the use of a group sequential-design method.13 The analysis was carried out on 752 events, resulting in an efficacy boundary for the hazard ratio of 0.833 (lower boundary) and a lack-of-efficacy boundary of 0.936 (upper boundary). At this interim analysis, the lack-of-efficacy boundary was crossed, and the committee recommended the release of results.

Design
Statistical mining of data collected on dietary habits of women with breast cancer. Diet in the 12–24 months before diagnosis was assessed with an extensive food frequency questionnaire, and confounders assessed from an epidemiologic interview and abstracted clinical data. Lignan intake was calculated using published food composition data.
Participants: 1,122 women, aged 35–79 years, diagnosed with breast cancer between 1996 and 2001. Data were collected as part of a study looking at lifetime alcohol consumption and breast cancer (WEB Study).

Study Methodology
The association between dietary lignan intake and survival was analyzed. Vital Status was tracked until the end of 2006. Extensive food questionnaires were used to track diet for 1–2 years before initial diagnosis. Lignan intake was calculated using current food composition tables. Hazard ratios (HR) for dietary lignan intake with all-cause and breast cancer mortality were calculated.

Outcome Measure
Vital status (living or deceased)

Key Findings
Postmenopausal women who consumed the most lignans had a significantly lower risk of dying from any cause and especially from breast cancer than women who ate only small amounts of lignan-containing foods. When upper versus lower quartiles of lignan intake were compared, there was a 51% (HR 0.49, 95% CI: 0.26–0.91) reduction of all-cause mortality in those consuming the higher lignan levels. These women had a 71% decreased risk of dying of breast cancer (HR 0.29, 95% CI: 0.11–0.76). High intakes of dried beans (HR 0.61, 95% CI: 0.36–1.03) may have also lowered risk of overall mortality and breast cancer mortality (HR 0.53, 95% CI: 0.24–1.14), though these numbers did not reach statistical significance.

Practice Implications
This is the first paper to examine the association of lignan intakes prior to breast cancer diagnosis and risk of dying. These findings suggest that we should actively promote consumption of lignan-containing foods, particularly in postmenopausal women.

In this study, the women with the highest reported intakes of total vegetables at baseline measure had an overall lower risk of recurrence and a lower risk of developing a new primary breast cancer.

In this study, the women with the highest reported intakes of total vegetables at baseline measure had an overall lower risk of recurrence and a lower risk of developing a new primary breast cancer. This effect was most pronounced in women taking tamoxifen, and the effect was the greatest in tamoxifen users who consumed the highest quantity of cruciferous vegetables. Essentially, this study suggests that vegetable intakes above the average US intakes increase the likelihood of disease-free survival in women taking tamoxifen. This beneficial effect is amplified with cruciferous vegetable intake.

The postulated mechanisms underlying this observed relationship include the synergistic role of indole-3-carbinol (I3C) found in broccoli with tamoxifen in inducing apoptosis over tamoxifen alone. Additionally, diindolylmethane (DIM), a metabolic end-product of I3C influences the metabolism of tamoxifen away from tamoxifen N-oxide, a relatively inactive metabolite, and toward its active metabolite, 4-hydroxy tamoxifen. Other studies have demonstrated that sulfurophane, another component of broccoli, induces apoptosis in breast cancer stem cells,1 an action that theoretically would complement and strengthen the antiproliferative effects of tamoxifen.

The findings in this secondary analysis are consistent with another recent study, which demonstrated that intake of 1 serving of raw broccoli, but not cooked broccoli or vegetables overall, at least once a month reduced the risk of dying from bladder cancer by 57% (HR for disease-specific death: 0.43; 95% CI: 0.25–0.74)2. This effect was attributed to isothiocyanates, which are destroyed in the cooking of broccoli.

The data from this secondary analysis is the latest addition to several studies elucidating the benefit of vegetable intake, and cruciferous vegetables in particular, on reducing the risk of cancer recurrence. The benefit of regular consumption of cruciferous vegetables, and broccoli in particular, on reducing the risk of breast cancer recurrence in tamoxifen users are worth notice. Tamoxifen has rapidly become part of standard care for women with estrogen receptor–positive breast cancer, which represents the majority of breast cancers. Thus, the inclusion of cruciferous vegetables in the daily diet of these women is important. The amount needed for this survival benefit is reasonable for most—a baseline of 0.5 servings per day—making this an acceptable strategy.

Limitations
This study was limited by the reliance upon self-reported data and thus the possibility of recall bias. Additionally, the data from this study cannot be generalized to other cohorts. Finally, as a secondary analysis, the conclusions should be verified in an independent study.

Pathologists characterize many aspects of breast cancer specimens but rarely pay much attention to the stroma. Whereas some tumors have more stroma than others, desmoplasia is only one of many properties that vary among individual ductal carcinomas. It seems logical that the pathology assessment should identify risk factors associated with rapid tumor progression; however, the pathologist focuses on issues that are more pragmatic: the extent of tumor, classification into histologic subtypes, and identification of properties that define therapeutic intervention, such as expression of estrogen receptor (ER) or HER2/neu. In this issue of The American Journal of Pathology, Conklin et al1 have demonstrated a stromal signature that has a correlation with progression. Although the potential exists for this signature to be used for prognosis, the main value of their correlation is to identify two important areas for further investigation. First, the stromal signature indicates a biologically significant process because it predicts how the tumor will behave. Defining this process is the first step in learning how to control it. Second, the stromal signature may indicate a novel mechanism of tumor progression if it is independent of other prognostic markers.

Multiphoton Microscopy

The new study is based on research from the Keely laboratory and others who used multiphoton microscopy to examine the structure of collagen fibers in tumors. Multiphoton microscopy (or two-photon microscopy) utilizes lasers that generate pulses of light with extremely high photon density in the near-infrared wavelength range of 700 to 1300 nm. For fluorescence imaging, the photon density is so high that near-simultaneous absorption of two photons by a fluorophore can occur, resulting in activation that is equivalent to absorption of a single photon with twice the energy. For example, with the laser tuned to 920 nm, simultaneous absorption of two photons is equivalent to absorption of a single 460-nm photon that can thus activate green fluorescent protein, which has a broad absorption peak around 500 nm. The nonlinear dependence of this effect on the square of photon density makes multiphoton fluorescence microscopy confocal in nature. It is also more efficient than ordinary fluorescence microscopy; there is less bleaching of fluorophores out of the plane of focus and deeper penetration into tissues because of the reduced scattering of near-infrared photons.

To image unstained collagen fibers in the tumor, Conklin et al used second harmonic generation, an additional but less well known advantage of multiphoton imaging. In second harmonic generation, periodic structures that are not centrosymmetriceg, collagen fibers—can act like frequency doubling crystals. In essence, two photons of one frequency enter the fiber, and one photon with exactly half the frequency leaves it. These second harmonic signals are mostly emitted in the same direction as the excitation light, but some are scattered backward and detected by the microscope used to deliver the excitation signal. The second harmonic signal is dependent on the presence of appropriately polarized structures including collagen fibers, myosin, and even microtubules.

The second harmonic signal for collagen fibers is detectable in paraffin sections of formalin-fixed tissue. Thus Conklin et al examined a standard breast cancer tissue microarray. The orientation of the collagen fibers was determined relative to the tumor cell masses to generate what the authors term the “tumor-associated collagen signature” or TACS. Different TACS categories correspond to various ways that the extracellular matrix can be organized with respect to the tumor cells. Originally these categories were defined by studying mammary tumor development in mouse models. TACS-1 arises first in early tumors with increased numbers of curved, apparently relaxed collagen fibers around the tumor. TACS-2 develops as the tumor grows larger. The surrounding fibers become straight and parallel to the surface of the tumor, probably reflecting stretching of the fibers due to the expansion of the tumor. TACS-3 reflects a significant reorganization of the matrix, so that straight matrix fibers now lead directly into the tumor cell mass. In TACS-3, the fibers can act as pathways along which cells can crawl, as has been seen in multiphoton imaging of metastatic tumors.

Thus TACS-3 is a potential marker of a highly invasive tumor, in which the reorganization of the matrix around the tumor apparently reflects a dramatic increase in the ability to spread and metastasize. The results by Conklin et al provide the first retrospective test of this hypothesis using a tissue microarray of 207 breast cancer patients with median clinical follow-up of 6 years. We will focus here on the most successful scoring method, termed Score 1. After each tissue core was divided into 14 areas, the presence of TACS-3 structures was scored separately by three pathologists. A receiver operating curve analysis determined the optimum threshold and demonstrated that detection of only one or two TACS-3 structures in a tissue core was sufficient.

In univariate analysis, TACS-3 scoring showed a significant association with both disease-specific survival and disease-free interval, each with a hazard ratio of 3. To test whether the TACS-3 scoring might provide a novel independent biomarker, the authors then performed a multivariate analysis. A wide range of markers were evaluated including tumor grade, size, patient age, estrogen receptor, progesterone receptor (PR), HER-2, and node status, among others. Within this group, TACS-3 was an independent prognostic marker for both disease-specific survival and disease-free interval, together with PR, ER, node status, and tumor size. Notably, TACS-3 did not correlate with any other markers tested in the analysis. Given these promising results, a classification and regression tree analysis was then performed for predicting 10-year disease-specific survival. Importantly, the TACS-3 score provided valuable prognostic information for patients with large ER-positive tumors. Patients with TACS-3-positive tumors showed a 40% reduction in survival compared with those who had TACS-3-negative tumors.

The TACS-3 scoring shows significant correlation with survival in an important category of breast cancer patients—those with ER-positive tumors that are >1.35 cm. The challenge is to translate this correlation to the pathology laboratory. The use of multiphoton microscopy for research studies of human cancer tissues, including freshly biopsied tissues, has been reported by a number of groups. Our opinion is that this practice is currently impractical for standard histopathology laboratories because of the expense of multiphoton microscopes and the amount of time required for the analysis. However, with the development of inexpensive laser sources, multiphoton microscopy may be accessible in the future. In considering less expensive substitutes, it is not exactly clear how TACS-3 signals detected by multiphoton microscopy correspond to standard histopathology, but there are several options for analyzing stroma. These options include selective demonstration of collagen fibers by Sirius red or reticulum stains or visualization along with cellular detail in H&E and trichrome stains.

Final Reflections

We suggest that two distinct processes exist: TACS-2 reflects stromal formation and organization controlled by the tumor cells, an orderly phase of growth and maturation that follows initial stromal penetration by tumor cells. In contrast, TACS-3 reflects invasion and disruption of preformed stroma by tumor cells. It therefore seems essential to define the histologic correlates of the two-photon TACS-3 detection so that the signatures can be assessed within a standard pathology work-up. The data by Conklin et al1 also imply a correlation with stromal expression of syndecan-1, a cell surface receptor that links extracellular matrix and cytoskeleton. Their description is a bit confusing, because an earlier article from this group characterized tumor cell expression of syndecan-1.18 The localization of syndecan-1 thus requires clarification, because immunohistochemical detection of syndecan-1 could prove to be an easily detected surrogate of TACS-3.

In summary, Conklin et al1 provide an admirable example of studies that bridge mouse cancer models and human diagnostic pathology. However, application of TACS-3 as a histologic or prognostic biomarker requires translation into parameters that fit into the routine pathology work-up. From a biological perspective, TACS-3 may represent a specific type of matrix organization controlled by tumor cells or a result of aggressive invasion. These alternatives define a valuable investigation into fundamental mechanisms of tumor progression.

On confirmation of the breast cancer from biopsy report, the doctors go through an extensive study about the extent or the stage of the cancer that will help to adopt the right type of treatment best suitable for the patient. Whether the cancer is localized or has spread to other parts of the body can be determined by staging that involves different types of screening including the blood test.

Bone scan is done by entering a small amount of radioactive substance into the blood vessel which gets collected in the bones, and the pictures taken confirm the spread of cancer to the bones.

CT scan of the breast cancer is done by taking pictures of the affected area through the X-rays to study whether the cancer has affected the lungs and liver.

Lymph node biopsy is done by inserting radioactive blue dye through a needle near the tumor or the nipple and checked for the cancerous lymphatic cells.

The different stages of breast cancer include –

Stage 0 – This stage can be also termed as Ductal Carcinoma in situ (DCIS), which indicates that the abnormal cells of the breast duct have not spread outside or invaded other local tissues. This stage cannot be termed cancerous but if untreated can turn into breast cancer.

Stage I indicates the earliest stage of breast cancer where the tumor is not more than 2 centimeters and the cancerous cells have affected only the breast tissue not spreading beyond.

Stage II – This may include features –

1. The tumor size not more than 2 centimeters but the cancer has affected the under arm lymph nodes or the cancer is localized.

2. The tumor size is of 2-5 centimeter and the cancer affecting the underarm lymph nodes.

Stage III comprises of three stages like Stage IIIA, IIIB and IIIC.

In Stage IIIA tumor is 5centimeters length across and the cancer has spread to the under arm lymph nodes. The cancer may spread to the single or attached lymph nodes under the arm and it may also affect the lymph nodes behind the breast bone.

In Stage IIIB the tumor may be of any size that grows along the chest wall or on the breast skin forming lumps and nodules. The under arm lymph nodes and the lymph nodes behind the breast bone may also be affected.

In this stage the inflammatory breast cancer may also occur with the breast becoming red and swollen.

In Stage IIIC the tumor may be of any size with the cancer spreading to the lymph nodes of under arm, behind the breast bone and also including the lymphatic nodes of the collarbone.

Stage IV or the metastatic change indicates the spread of the breast cancer to other parts of the body like liver and bones.

Breast cancer is one of the leading killer cancers for women. Normally people know that it is only women that are susceptible to this. But did you know that there are many cases where men have also gotten this type of cancer? As this is very common form of cancer so each person needs to educate themselves about prevention of breast cancer. There is no definite way to prevent breast cancer but you can do much to reduce your risk of developing it significantly. Especially women should concentrate on keeping breast health through healthy diet and exercise to prevent breast cancer.
Following are the few tips to lower your chances of breast cancer:

1. Daily physical activity is very essential. It is not only important for overall health; it also can reduce the risk of breast cancer.
2. You should maintain your body weight. The main reason to significantly increase breast cancer risk is basically weight gain in midlife.
3. Women who gain weight in mature age are at a higher risk for than women who have been overweight since babyhood.
4. Women who breastfeed their offspring may have a somewhat lower risk of developing breast cancer.
5. It is essential to regular intake of natural vitamins, minerals and antioxidants. You should take eat as many fruits and vegetables as possible. It helps to reduce the risk of breast cancer.

Usually, a woman who had cancer in one breast has more chances of developing cancer in the opposite breast. It is preferable to follow a healthy living style to be secure from the return of breast cancer.
These are some tips if you follow these than these will definitely increase your chances to prevent breast cancer.

Due to the increased life expectancy increasing number of people affected by cancer. In adults, very often operate on cancers that affect organs such as lung, pancreas or colon cancer. In children, however, carcinomas occur as well as never before. For them, the leukemia is the most common form of cancer.

Men are affected statistics resulted almost twice as often, subject to age this is the 68th Year of life lies.

A healthy diet and regular check-ups can act prophylactically, or leave a disease seen very quickly. The earlier cancer is detected, the greater are the chances of recovery.

In women, breast cancer and cervical cancer is a very common form. Here, too, through regular examinations quickly detect and treat cancer. In order to have breast cancer preventions, certain hormones (contraceptive pill) is very well proven and especially women, whose ancestors had ill with cancer, regular screening should to be taken over by the health perceptions.

For breast cancer prevention also includes the regular scanning. Exactly how this works, will explain to a gynecologist. These small lumps or other breast tissue or under the arm can be felt much quicker. Also, the mammography is one of the screening tests. This investigation form is particularly suitable for women over 40 years.

In younger women, this investigation does not arise often incorrect results and therefore occurs in women under 40 years, only less frequent mammography as an investigation into question. But if breast cancer runs if your family, and your grandmother and / or mother had it, you should get checked more often.

Better safe than sorry when it comes to your health.

The men of any age may develop breast cancer, but is usually detected in men between 45 and 65 years of age. Breast cancer found in men is less than 1% of all cases of breast cancer. Although rare, the inflammatory breast cancer found in males is a very aggressive cancer that grows quickly. It’s called inflammatory because cancer cells block the lymph vessels and this is manifested in the skin, which becomes thick and hollowed, the appearance is similar to that of an orange peel.

You may find the following types of breast cancer in males:

• Infiltrating ductal carcinoma: Cancer that has spread beyond the cells lining the breast ducts. This is the kind suffered by the majority of men with breast cancer.
• Ductal carcinoma in situ: Abnormal cells found in the lining of a duct, also called intraductal carcinoma.
• Inflammatory breast cancer: A type of cancer in which the breast looks red and swollen and feels warm.
• Paget’s disease of the nipple: the surface of an underlying tumor ducts underneath the nipple.

Inflammatory breast cancer can spread in just a few weeks, is often mistaken for other things like a rash or infection. The symptoms are:

• Redness, swelling and warmth in the breast
• Red skin, purple or bruised
• Skin with bumps and / or marks as an orange
• Burning, pain and tenderness
• Increased breast size and an inverted nipple

Because usually this cancer does not form like a regular ball of tissue, but it spreadsthroughout the breast tissue right a way. This is why it is very difficult to detect with a mammogram alone, and the magnetic resonance imaging and biopsies can not usually diagnose it accurately either. However, surgical biopsy and positron emission tomography (PET) can be used effectively to detect it. In the near future, PET may be the most important diagnostic test for the inflammatory breast cancer. Although still under evaluation, Doctors have found that PET is able to see more inflammatory breast cancer, including lymph nodes removed from the breast, which will determine the presence of metastases at diagnosis better than other test.

Certain factors affect prognosis (chance of recovery) and treatment options. 
The prognosis and treatment options depend on the following aspects:

• The stage of cancer (if located in the breast only or has spread to other parts in the body).
• The type of breast cancer.
• The concentration of estrogen receptors and progesterone receptors in tumor tissue.
• If cancer is also found in the other breast also.
• The age and general health of the patient.

I hope that you find this informayion helpful.

Breast cancer can spread to any part of your body through the blood and lymphatic system. The metastasis of breast cancer cells is what makes the disease very dangerous. Metastasis means the cancer cells have traveled from the place of origin, i.e. the breast, to other parts of the body.

When the cancer cells travel from the breast to the underarm lymph nodes, it is still considered to be early stages of breast cancer and it has a high potential to be completely cured. With surgery and treatment there is a very high chance that all the disease can be completely eradicated from the body.

When the cancer cells travel beyond the lymph nodes to other distant parts of the body, the patient is said to have distant metastasis. The bones, lungs and liver are the most commonly affected places in the body that breast cancer cells spread to. Though treatment is available for breast cancer and for metastasic breast cancer, once the cancer has traveled beyond the breast and underarm lymph nodules, it can no longer be totally cured.

Scientists have recently discovered a molecule that could be the main reason behind the spreading of breast cancer cells to different parts of the body. The molecule known as Brk is found in almost 60% of breast cancers and they accelerate the growth of the tumor cells, encouraging metastasis to other parts of the body.

The study was conducted on breast cancer patients who had extremely poor responses to the treatments. The Brk molecule was found in very high concentration in these patients, which means that not only does it cause the cancer to grow more aggressively; it also encourages its rapid spread to other parts of the body.

The study also came out with another crucial finding. The tumor cells died when the Brk molecule was inhibited, but the cancer cells re-emerged when the molecule was introduced again. This points to a significant level of involvement that the Brk molecule has in encouraging the breast cancer cells to survive, grow and spread.

Scientists are currently studying how exactly the Brk molecule promotes the growth of breast cancer cells so that they can develop ways to prevent that from happening. The findings are quote encouraging and shed new light on the age old battle of mankind against cancer.

Practices on this cancer prevention are only for women with moderate to high breast cancer risk. There are still no guidelines for the prevention for women with average risk.

However, how can we identify the group of women at known risk in general population? Thus, it is important for us to know whether we are in risk of breast cancer by knowing the risk factors and do the early detection steps frequently.

In General
Generally, we can do some prevention steps in our daily life no matter we are in risk or not. Leading a healthy lifestyle is an essential prevention step for all the cancer.

1. It is advised that women need to maintain a healthy body weight throughout their daily life without consuming high fat food.

2. Women have to do some regular physical activities such as jogging, swimming and so on.

3. Breastfeeding is a good practice to prevent the breast cancer.

4. Consume diets that rich in grains, fruits and vegetables. Less meat in diet will be too good to be practiced.

5. Moderate use of alcoholic beverages. It is too good not to consume the alcoholic beverages at all.

6. Minimize yourself from the exposure to exogenous hormones.

7. Reduce the sugars in the diet.

Women with Moderate to High Risk
There are several ways for the prevention of this kind of cancer in women at significantly increased risk.

Who are those with moderate to high risk in breast cancer?

• Women who are the carriers of BRCA1/BRCA2 mutation.
• Women with multiple affected relative cancer presenting at early age.
• Women with family history of this kind of cancer and so on.

There are many options for the women in risk to prevent from breast cancer. Most of the strategies are to remove the tissue which may become cancerous and decrease the endogenous hormone exposure. The most common is bilateral prophylactic mastectomy.

In conclusion, it is important for us to recognize the group of women with high risk or moderate risk who will ultimately develop this type of cancers. There are many risk assessment can be done through the cancer research. This will reduce the need for many women to unnecessarily undergo aggressive surgery.