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Breast cancer screening refers to testing otherwise-healthy women for breast cancer in an attempt to achieve an earlier diagnosis under the assumption that early detection will improve outcomes. A number of screening tests have been employed including clinical and self breast exams, mammography, genetic screening, ultrasound, and magnetic resonance imaging.
A clinical or self breast exam involves feeling the breast for lumps or other abnormalities. Clinical breast exams are performed by health care providers, while self-breast exams are performed by the person themselves. Evidence does not support the effectiveness of either type of breast exam, as by the time a lump is large enough to be found it is likely to have been growing for several years and thus soon be large enough to be found without an exam. Mammographic screening for breast cancer uses X-rays to examine the breast for any uncharacteristic masses or lumps. During a screening, the breast is compressed and a technician takes photos from multiple angles. A general mammogram takes photos of the entire breast, while a diagnostic mammogram focuses on a specific lump or area of concern.
A number of national bodies recommend breast cancer screening. For the average woman, the U.S. Preventive Services Task Force recommends mammography every two years in women between the ages of 50 and 74, the Council of Europe recommends mammography between 50 and 69 with most programs using a 2-year frequency, and in Canada screening is recommended between the ages of 50 and 74 at a frequency of 2 to 3 years. These task force reports point out that in addition to unnecessary surgery and anxiety, the risks of more frequent mammograms include a small but significant increase in breast cancer induced by radiation.
The Cochrane collaboration (2013) states that the best quality evidence neither demonstrates a reduction in cancer specific, nor a reduction in all cause mortality from screening mammography. When less rigorous trials are added to the analysis there is a reduction in mortality due to breast cancer of 0.05% (a decrease of 1 in 2000 deaths from breast cancer over 10 years or a relative decrease of 15% from breast cancer). Screening over 10 years results in a 30% increase in rates of over-diagnosis and over-treatment (3 to 14 per 1000) and more than half will have at least one falsely positive test. This has resulted in the view that it is not clear whether mammography screening does more good or harm. Cochrane states that, due to recent improvements in breast cancer treatment, and the risks of false positives from breast cancer screening leading to unnecessary treatment, "it therefore no longer seems beneficial to attend for breast cancer screening" at any age. Whether MRI as a screening method has greater harms or benefits when compared to standard mammography is not known.
80% of cases in the United States are diagnosed by mammography screening.
The selective estrogen receptor modulators (such as tamoxifen) reduce the risk of breast cancer but increase the risk of thromboembolism and endometrial cancer. There is no overall change in the risk of death. They are thus not recommended for the prevention of breast cancer in women at average risk but may be offered for those at high risk. The benefit of breast cancer reduction continues for at least five years after stopping a course of treatment with these medications.
Several tests are used to diagnose vaginal cancer, including:
- Physical exam and history
- Pelvic exam
- Pap smear
- Biopsy
- Colposcopy
Recommendations for women with vaginal cancer is not to have routine surveillance imaging to monitor the cancer unless they have new symptoms or rising tumor markers. Imaging without these indications is discouraged because it is unlikely to detect a recurrence or improve survival, and because it has its own costs and side effects. MRI provides visualization of the extent of vaginal cancer.
Prevention
The only reliable method of diagnosis is full-thickness skin biopsy. Mammography, MRI or ultrasound often show suspicious signs; however in a significant proportion of cases they would miss a diagnosis.
Clinical presentation is typical only in 50-75% of cases; and many other conditions such as mastitis or even heart insufficiency can mimic the typical symptoms of Inflammatory Breast Cancer.
Temporary regression or fluctuation of symptoms, spontaneous or in response to conventional treatment or hormonal events should not be considered of any significance in diagnosis. Treatment with antibiotics or progesterone have been observed to cause a temporary regression of symptoms in some cases.
Triple-negative breast cancer accounts for approximately 15%-25% of all breast cancer cases. The overall proportion of TNBC is very similar in all age groups. Younger women have a higher rate of basal or BRCA related TNBC while older women have a higher proportion of apocrine, normal-like and rare subtypes including neuroendocrine TNBC.
Among younger women, African American and Hispanic women have a higher risk of TNBC, with African Americans facing worse prognosis than other ethnic groups.
In 2009, a case-control study of 187 triple-negative breast cancer patients described a 2.5 increased risk for triple-negative breast cancer in women who used oral contraceptives (OCs) for more than one year compared to women who used OCs for less than one year or never. The increased risk for triple-negative breast cancer was 4.2 among women 40 years of age or younger who used OCs for more than one year, while there was no increased risk for women between the ages of 41 and 45. Also, as duration of OC use increased, triple-negative breast cancer risk increased.
Typically self-examination leads to the detection of a lump in the breast which requires further investigation. Other less common symptoms include nipple discharge, nipple retraction. swelling of the breast, or a skin lesion such as an ulcer. Ultrasound and mammography may be used for its further definition. The lump can be examined either by a needle biopsy where a thin needle is placed into the lump to extract some tissue or by an excisional biopsy where under local anesthesia a small skin cut is made and the lump is removed. Not all palpable lesions in the male breast are cancerous, for instance a biopsy may reveal a benign fibroadenoma. In a larger study from Finland the average size of a male breast cancer lesion was 1.8 cm. Beside the histologic examination estrogen and progesterone receptor studies are performed. Further, the HER2 test is used to check for a growth factor protein. Its activity can be increased in active cancer cells and helps determine if monoclonal antibody therapy (i.e. Trastuzumab) may be useful.
Male breast cancer can recur locally after therapy, or can become metastatic.
In addition to TNM staging surgical staging for breast cancer is used; it is the same as in female breast cancer and facilitates treatment and analysis.
Staging is designed to help organize the different treatment plans and to understand the prognosis better. Staging for IBC has been adapted to meet the specific characteristics of the disease. IBC is typically diagnosed in one of these stages:
- Stage IIIB - at least 1/3 of the skin of the breast is affected, and may have spread to tissues near the breast, such as the skin or chest wall, including the ribs and muscles in the chest. The cancer may have spread to lymph nodes within the breast or under the arm.
- Stage IIIC - N3 nodal involvement with an inflamed breast will upgrade the disease from Stage IIIB to Stage IIIC.
- Stage IV means that the cancer has spread to other organs. These can include the bones, lungs, liver, and/or brain.
While the histopathologic features and molecular features of ADH are that of (low-grade) DCIS, its clinical behaviour, unlike low-grade DCIS, is substantially better; thus, the more aggressive treatment for DCIS is not justified. In oncology in general, it is observed that tumour size is often strongly predictive of the clinical behaviour and, thus, a number of cancers (e.g. adenocarcinoma of the lung, papillary renal cell carcinoma) are defined, in part, on the basis of a minimum size.
The rate at which breast cancer (ductal carcinoma in situ "or" invasive mammary carcinoma (all breast cancer except DCIS and LCIS)) is found at the time of a surgical (excisional) biopsy, following the diagnosis of ADH on a core (needle) biopsy varies considerably from hospital-to-hospital (range 4-54%). In two large studies, the conversion of an ADH on core biopsy to breast cancer on surgical excision, known as "up-grading", is approximately 30%.
Because DCIS is normally found early and it is treated or managed, it is difficult to say what occurs if left untreated. About 2% of women who are diagnosed with this condition and treated died within 10 years. Biomarkers can identify which women who were initially diagnosed with DCIS are at high or low risk of subsequent invasive cancer.
The presence of a radial scar on imaging mandates a percutaneous core biopsy for histologic diagnosis. Excisional biopsy is usually recommended for radial scar, although it has been argued that core biopsy evaluation and surveillance may be appropriate in selected patients.
A fibroadenoma is usually diagnosed through clinical examination, ultrasound or mammography, and often a needle biopsy sample of the lump.
In the detection of bone metastases, skeletal scintigraphy (bone scan) is very sensitive and is recommended as the first imaging study in asymptomatic individuals with suspected breast-cancer metastases. X-ray radiography is recommended if there is abnormal radionuclide uptake from the bone scan and in assessing the risk of pathological fractures, and is recommended as the initial imaging study in patients with bone pain. MRI or the combination PET-CT may be considered for cases of abnormal radionuclide uptake on bone scan, when radiography does not give an acceptably clear result.
Historically, the combination of external-beam radiation therapy (EBRT) has been the most common treatment for vaginal cancer. In early stages of vaginal cancer, surgery also has some benefit. This management and treatment is less effective for those with advanced stages of cancer but works well in early stages with high rates of cure. Advanced vaginal cancer only has a 5-year survival rates of 52.2%, 42.5% and 20.5% for patients with stage II, III and IVa disease. Newer treatments for advanced stages of ovarian have been developed. These utilize concurrent carboplatin plus paclitaxel, EBRT and high-dose-rate interstitial brachytherapy (HDR-ISBT).
When the chance of surgical removal of all cancerous tissue is very low or when the surgery has a chance of damaging the bladder, vagina or bowel, radiation therapy is used. When a tumor is less than 4 cm in diameter, radiation therapy provides excellent results. In these instances, the 5-year survival rate is greater than 80%. Treatments are individualized due to the rarity of vaginal cancer studies.
Angiogenesis and EGFR (HER-1) inhibitors are frequently tested in experimental settings and have shown efficacy. Treatment modalities are not sufficiently established for normal use, and it is unclear in which stage they are best used and which patients would profit.
By 2009 A number of new strategies for TNBC were being tested in clinical trials, including the PARP inhibitor BSI 201, NK012.
A novel antibody-drug conjugate known as Glembatumumab vedotin (CDX-011), which targets the protein GPNMB, has also shown encouraging clinical trial results in 2009.
PARP inhibitors had shown some promise in early trials but failed in some later trials.
Nov 2013: An accelerated approval Phase II clinical trial (METRIC) investigating glembatumumab vedotin versus capecitabine has begun, expected to enroll 300 patients with GPNMB-expressing metastatic TNBC.
Three early stage trials reported TNBC results in June 2016, for IMMU-132, Vantictumab, and atezolizumab in combination with the chemotherapy nab-paclitaxel.
In order to establish whether the lump is a cyst or not, several imaging tests may be performed. Mammography is usually the first imaging test to be ordered when unusual breast changes have been detected during a physical examination. A diagnostic mammography consists in a series of x-rays that provide clear images of specific areas of the breast.
Ultrasounds and MRIs are commonly performed in conjunction with mammographies as they produce clear images of the breast and clearly distinguish between fluid-filled breast cysts and solid masses. The ultrasound and MRI exams can better evaluate dense tissue of the breast; hence it is often undergone by young patients, under 30 years old.
Recommended tests are a mammogram and a biopsy to confirm the diagnosis, and cytopathology may also be helpful. Paget's disease is difficult to diagnose due to its resemblance to dermatitis and eczema; even in patients after ductal carcinoma in situ surgery. Eczema tends to affect the areola first, and then the nipple, whereas Paget's spreads from the nipple.
During a physical examination, the doctor examines the unusual areas of the breast, especially the appearance of the skin on and around the nipples and feeling for any lumps or areas of thickening.
The most common test used to diagnose Paget's disease is the biopsy, removal of a tissue sample from the affected area which is then examined under the microscope by a pathologist, who distinguishes Paget cells from other cell types by staining tissues to identify specific cells (immunohistochemistry). Samples of nipple discharge may also be examined under the microscope to determine whether Paget cells are present.
Imprint or scrape cytopathology may be useful: scraping cells from the affected area, or pressing them onto a glass slide to be examined under the microscope.
On average, a woman may experience signs and symptoms for six to eight months before a diagnosis is made.
Because this is a rare tumor, not many family physicians or oncologists are familiar with this disease. DSRCT in young patients can be mistaken for other abdominal tumors including rhabdomyosarcoma, neuroblastoma, and mesenteric carcinoid. In older patients DSRCT can resemble lymphoma, peritoneal mesothelioma, and peritoneal carcinomatosis. In males DSRCT may be mistaken for germ cell or testicular cancer while in females DSRCT can be mistaken for Ovarian cancer. DSRCT shares characteristics with other small-round blue cell cancers including Ewing's sarcoma, acute leukemia, small cell mesothelioma, neuroblastoma, primitive neuroectodermal tumor, rhabdomyosarcoma, and Wilms' tumor.
Diagnosis is mostly done based on symptoms after exclusion of breast cancer. Nipple fluid aspiration can be used to classify cyst type (and to some extent improve breast cancer risk prediction) but it is rarely used in practice. Biopsy or fine needle aspiration are rarely warranted.
Fibrocystic breast disease is primarily diagnosed based on the symptoms, clinical breast exam and on a physical exam. During this examination, the doctor checks for unusual areas in the breasts, both visually and manually. Also, the lymph nodes in the axilla area and lower neck are examined. A complete and accurate medical history is also helpful in diagnosing this condition. If the patient's medical history and physical exam findings are consistent with normal breast changes, no additional tests are considered but otherwise the patient will be asked to return a few weeks later for reassessment. Women may detect lumps in their breasts during self-examination as well.
DSRCT is frequently misdiagnosed. Adult patients should always be referred to a sarcoma specialist. This is an aggressive, rare, fast spreading tumor and both pediatric and adult patients should be treated at a sarcoma center.
There is no standard protocol for the disease; however, recent journals and studies have reported that some patients respond to high-dose (P6 Protocol) chemotherapy, maintenance chemotherapy, debulking operation, cytoreductive surgery, and radiation therapy. Other treatment options include: hematopoietic stem cell transplantation, intensity-modulated radiation Therapy, radiofrequency ablation, stereotactic body radiation therapy, intraperitoneal hyperthermic chemoperfusion, and clinical trials.
A meta analysis of cohort studies of alcohol consumption and breast cancer mortality showed no association between alcohol consumption before or after breast cancer diagnosis and recurrence after treatment.
The FDA has approved cryoablation of a fibroadenoma as a safe, effective and minimally-invasive alternative to open surgical removal in 2001. In the procedure, ultrasound imaging is used to guide a probe into the mass of breast tissue. Extremely cold temperatures are then used to destroy the abnormal cells, and over time the cells are reabsorbed into the body. The procedure can be performed as an outpatient surgery using local anesthesia only, and leaves substantially less scarring than open surgical procedures and no breast tissue deformation.
The American Society of Breast Surgeons recommends the following criteria to establish a patient as a candidate for cryoablation of a fibroadenoma:
1. The lesion must be sonographically visible.
2. The diagnosis of a fibroadenoma must be confirmed histologically.
3. The lesion should be less than 4 cm in diameter.
Metastasis is a complex and interconnected multi-step process. Each step in the process is a potential target for therapies to prevent or reduce metastasis. Those steps which have a good clinical window are the best targets for therapy. Each event in metastasis is highly regulated and requires a synergistic activation of different ECM proteins, growth factors and so on. Although the occasional patient with metastatic breast cancer benefits from surgical resection of an isolated metastasis and most patients receive radiotherapy (often for palliation alone) during the course of their disease, the treatment of metastatic breast carcinoma typically involves the use of systemic therapy.