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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.
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.
Screening by hysteroscopy to obtain cell samples obtained for histological examination is being developed. This is similar to the current pap smear that is used to detect cervical cancer. The UK Collaborative Trial of Ovarian Cancer Screening is testing a screening technique that combines CA-125 blood tests with transvaginal ultrasound. Other studies suggest that this screening procedure may be effective. However, it's not yet clear if this approach could actually help to save lives—the full results of the trial will be published in 2015. One major problem with screening is no clear progression of the disease from stage I (noninvasive) to stage III (invasive) is seen, and it may not be possible to find cancers before they reach stage III. Another problem is that screening methods tend to find too many suspicious lesions, most of which are not cancer, but malignancy can only be assessed with surgery. The ROCA method combined with transvaginal ultrasonography is being researched in high-risk women to determine if it is a viable screening method. It is also being investigated in normal-risk women as it has shown promise in the wider population. Studies are also in progress to determine if screening helps detect cancer earlier in people with BRCA mutations.
Research into various prognostic factors for ovarian cancer is also going on. Recent research shows that thrombocytosis predicts lower survival and higher stage cancer. Ongoing research is also investigating the benefits of surgery for recurrent ovarian cancer.
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.
Routine screening of asymptomatic people is not indicated, since the disease is highly curable in its early, symptomatic stages. Instead, women, particularly menopausal women, should be aware of the symptoms and risk factors of endometrial cancer. A cervical screening test, such as a Pap smear, is not a useful diagnostic tool for endometrial cancer because the smear will be normal 50% of the time. A Pap smear can detect disease that has spread to the cervix. Results from a pelvic examination are frequently normal, especially in the early stages of disease. Changes in the size, shape or consistency of the uterus and/or its surrounding, supporting structures may exist when the disease is more advanced. Cervical stenosis, the narrowing of the cervical opening, is a sign of endometrial cancer when pus or blood is found collected in the uterus (pyometra or hematometra).
Women with Lynch syndrome should begin to have annual biopsy screening at the age of 35. Some women with Lynch syndrome elect to have a prophylactic hysterectomy and salpingo-oophorectomy to greatly reduce the risk of endometrial and ovarian cancer.
Transvaginal ultrasound to examine the endometrial thickness in women with postmenopausal bleeding is increasingly being used to aid in the diagnosis of endometrial cancer in the United States. In the United Kingdom, both an endometrial biopsy and a transvaginal ultrasound used in conjunction are the standard of care for diagnosing endometrial cancer. The homogeneity of the tissue visible on transvaginal ultrasound can help to indicate whether the thickness is cancerous. Ultrasound findings alone are not conclusive in cases of endometrial cancer, so another screening method (for example endometrial biopsy) must be used in conjunction. Other imaging studies are of limited use. CT scans are used for preoperative imaging of tumors that appear advanced on physical exam or have a high-risk subtype (at high risk of metastasis). They can also be used to investigate extrapelvic disease. An MRI can be of some use in determining if the cancer has spread to the cervix or if it is an endocervical adenocarcinoma. MRI is also useful for examining the nearby lymph nodes.
Dilation and curettage or an endometrial biopsy are used to obtain a tissue sample for histological examination. Endometrial biopsy is the less invasive option, but it may not give conclusive results every time. Hysteroscopy only shows the gross anatomy of the endometrium, which is often not indicative of cancer, and is therefore not used, unless in conjunction with a biopsy. Hysteroscopy can be used to confirm a diagnosis of cancer. New evidence shows that D&C has a higher false negative rate than endometrial biopsy.
Before treatment is begun, several other investigations are recommended. These include a chest x-ray, liver function tests, kidney function tests, and a test for levels of CA-125, a tumor marker that can be elevated in endometrial cancer.
The tumor marker CA-125 is frequently elevated in endometrial cancer and can be used to monitor response to treatment, particularly in serous cell cancer or advanced disease. Periodic MRIs or CT scans may be recommended in advanced disease and women with a history of endometrial cancer should receive more frequent pelvic examinations for the five years following treatment. Examinations conducted every three to four months are recommended for the first two years following treatment, and every six months for the next three years.
Women with endometrial cancer should not have routine surveillance imaging to monitor the cancer unless new symptoms appear or tumor markers begin rising. 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. If a recurrence is suspected, PET/CT scanning is recommended.
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.
Standard treatment is surgery with adjuvant chemotherapy and radiotherapy. As a variation, neoadjuvant chemotherapy is very frequently used for triple-negative breast cancers. This allows for a higher rate of breast-conserving surgeries and by evaluating the response to the chemotherapy gives important clues about the individual responsiveness of the particular cancer to chemotherapy.
In addition to chemotherapy, an additive called Didox can be added to aid in the reduction of drug resistance and further treatment efforts. Didox is used to inhibit ribonucleotide reductase M2 (RRM2) which contributes to the cells resistance of the chemotherapy treatment resulting in a large number of relapse (Wilson 2016). RRM2 is upregulated within these specific Triple Negative cancer cells leading to a higher rate of drug resistance and inability to slow or stop the tumor progression which leads to more aggressive forms of triple negative breast cancer that are often fatal (Wilson 2016).
TNBCs are generally very susceptible to chemotherapy. In some cases, however, early complete response does not correlate with overall survival. This makes it particularly complicated to find the optimal chemotherapy. Adding a taxane to the chemotherapy appears to improve outcome substantially.
"BRCA1"-related triple-negative breast cancer appear to be particularly susceptible to chemotherapy including platinum-based agents and taxanes.
Although mutations in single genes were not individually predictive, TNBC tumors bearing mutations in genes involved in the androgen receptor (AR) and FOXA1 pathways were much more sensitive to chemotherapy. Mutations in the AR/FOXA1 pathway provide a novel marker for identifying chemosensitive TNBC patients who may benefit from current standard-of-care chemotherapy regimens. Mutations that lowered the levels of functional BRCA1 or BRCA2 RNA were associated with significantly better survival outcomes. This BRCA deficience signature define a new, highly chemosensitive subtype of TNBC. BRCA-deficient TNBC tumors have a higher rate of clonal mutation burden, defined as more clonal tumors with a higher number of mutations per clone, and are also associated with a higher level of immune activation, which may explain their greater chemosensitivity.
For many patients with stage I cancer, adjuvant (preventative) therapy following surgery may not be appropriate and patients will undergo surveillance instead. The form this surveillance takes, e.g. the type and frequency of investigations and the length time it should continue, will depend on the type of cancer (non-seminoma or seminoma), but the aim is to avoid unnecessary treatments in the many patients who are cured by their surgery, and ensure that any relapses with metastases (secondary cancers) are detected early and cured. This approach ensures that chemotherapy and or radiotherapy is only given to the patients that need it. The number of patients ultimately cured is the same using surveillance as post-operative “adjuvant” treatments, but the patients have to be prepared to follow a prolonged series of visits and tests.
For both non-seminomas and seminomas, surveillance tests generally include physical examination, blood tests for tumor markers, chest x-rays and CT scanning. However, the requirements of a surveillance program differ according to the type of disease since, for seminoma patients, relapses can occur later and blood tests are not as good at indicating relapse.
CT scans are performed on the abdomen (and sometimes the pelvis) and also the chest in some hospitals. Chest x-rays are increasingly preferred for the lungs as they give sufficient detail combined with a lower false-positive rate and significantly smaller radiation dose than CT.
The frequency of CT scans during surveillance should ensure that relapses are detected at an early stage while minimizing the radiation exposure.
For patients treated for stage I non-seminoma, a randomised trial (Medical Research Council TE08) showed that, when combined with the standard surveillance tests described above, 2 CT scans at 3 and 12 months were as good as 5 over 2 years in detecting relapse at an early stage.
For patients treated for stage I seminoma who choose surveillance rather than undergoing adjuvant therapy, there have been no randomized trials to determine the optimum frequency of scans and visits, and the schedules vary very widely across the world, and within individual countries. In the UK there is an ongoing clinical trial called TRISST. This is assessing how often scans should take place and whether magnetic resonance imaging (MRI) can be used instead of CT scans. MRI is being investigated because it does not expose the patient to radiation and so, if it is shown to be as good at detecting relapses, it may be preferable to CT.
For more advanced stages of testicular cancer, and for those cases in which radiation therapy or chemotherapy was administered, the extent of monitoring (tests) after treatment will vary on the basis of the circumstances, but normally should be done for five years in uncomplicated cases and for longer in those with higher risks of relapse.
After removal, the testicle is fixed with Bouin's solution because it better conserves some morphological details such as nuclear conformation. Then the testicular tumor is staged by a pathologist according to the TNM Classification of Malignant Tumors as published in the AJCC Cancer Staging Manual. Testicular cancer is categorized as being in one of three stages (which have subclassifications). The size of the tumor in the testis is irrelevant to staging. In broad terms, testicular cancer is staged as follows:
- Stage I: the cancer remains localized to the testis.
- Stage II: the cancer involves the testis and metastasis to retroperitoneal and/or paraaortic lymph nodes (lymph nodes below the diaphragm).
- Stage III: the cancer involves the testis and metastasis beyond the retroperitoneal and paraaortic lymph nodes. Stage 3 is further subdivided into non-bulky stage 3 and bulky stage 3.
Further information on the detailed staging system is available on the website of the American Cancer Society.
In some population studies moderate alcohol consumption is associated with increase the breast cancer risk.
In contrast, research by the Danish National Institute for Public Health, comprising 13,074 women aged 20 to 91 years, found that moderate drinking had virtually no effect on breast cancer risk.
Studies that control for screening incidence show no association with moderate drinking and breast cancer, e.g.. Moderate drinkers tend to screen more which results in more diagnoses of breast cancer, including mis-diagnoses. A recent study of 23 years of breast cancer screening in the Netherlands concluded that 50% of diagnoses were over-diagnoses.
Hurthle cell thyroid cancer is often considered a variant of follicular cell carcinoma. Hurthle cell forms are more likely than follicular carcinomas to be bilateral and multifocal and to metastasize to lymph nodes. Like follicular carcinoma, unilateral hemithyroidectomy is performed for non-invasive disease, and total thyroidectomy for invasive disease.
Some studies have shown that thyroglobulin (Tg) testing combined with neck ultrasound is more productive in finding disease recurrence than full- or whole-body scans (WBS) using radioactive iodine. However, current protocol (in the USA) suggests a small number of clean annual WBS are required before relying on Tg testing plus neck ultrasound. When needed, whole body scans consist of withdrawal from thyroxine medication and/or injection of recombinant human Thyroid stimulating hormone (TSH). In both cases, a low iodine diet regimen must also be followed to optimize the takeup of the radioactive iodine dose. Low dose radioiodine of a few millicuries is administered. Full body nuclear medicine scan follows using a gamma camera. Scan doses of radioactive iodine may be I or I.
Recombinant human TSH, commercial name Thyrogen, is produced in cell culture from genetically engineered hamster cells.
In the older literature survival rates have been given as 35–50% for Stage I–II and 0–15% for Stage III and IV UPSC, More recently it was reported that forty-two percent of 138 patients were found disease-free at five years.
In 2009, the journal of "Gynecologic Oncology" reported the following 5-year survival rates based upon stage of cancer:
- Stage I: 50% - 80%
- Stage II: 50%
- Stage III: 20%
- Stage IV: 5% - 10%
Prognosis of the UPSC is affected by age, stage, and histology as well as treatment.
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.
The breast biopsy is usually the test used to confirm the suspected diagnosing. After imaging tests have been performed and have revealed unusual areas or lumps in the breast, a breast biopsy will be ordered. This test consists in removing a sample of breast tissue which is then looked at under a microscope. The specialist analyzing the tissue sample will be able to conclude if the breast changes are benign or malignant or whether breast fibrocystic disease is present.
There are four main types of breast biopsies that may be performed. A fine-needle aspiration biopsy is usually ordered when the doctor is almost certain that the lump is a cyst. This test is generally performed in conjunction with an ultrasound which is helpful in guiding the needle into a small or hard to find lump. The procedure is painless and it consists in inserting a thin needle into the breast tissue while the lump is palpated.
The core-needle biopsy is normally performed under local anesthesia and in a physician's office. The needle used in this procedure is slightly larger than the one used for a fine-needle biopsy because the procedure is intended to remove a small cylinder of tissue that will be sent to the laboratory for further examination.
A newer type of breast biopsy is the stereotactic biopsy that relies on a three-dimensional x-ray to guide the needle biopsy of non-palpable mass. The biopsy is performed in a similar manner, by using a needle to remove tissue sample but locating the specific area of the breast is done by x-raying the breast by two different angles. Surgical biopsy is a procedure performed to remove the entire lump or a part of it for laboratory analyzing. It may be painful and it is done under local anesthesia.
Since Krukenberg tumors are secondary (metastatic), management might logically be driven by identifying and treating the primary cancer. The optimal treatment of Krukenberg tumors is unclear. The role of surgical resection has not been adequately addressed but if metastasis is limited to the ovaries, surgery may improve survival. The role of chemotherapy and/or radiotherapy is uncertain but may sometimes be beneficial.