Our knowledge of cancer is always expanding. Researchers and healthcare professionals take the knowledge gained from research studies and use it to develop better practices that will help prevent, detect and treat breast cancer, as well as improve the quality of life of people with breast cancer.
The following information is a selection of research showing promise for breast cancer.
Risk reduction
Risk reduction strategies may reduce the chance of developing cancer.
Noteworthy research includes:
- Chemoprevention is the use of substances to reduce the risk of cancer developing. Changes in the amount or balance of the female hormone estrogen can increase breast cancer risk. As a result, much of the research into risk reduction has focused on strategies to lower the amount of estrogen in the body or block its effects.
- The ExCel research study is a phase III breast cancer prevention trial. It is testing exemestane (Aromasin), which is a drug that decreases the amount of estrogen made by the body. Women in the study were randomly chosen to receive either exemestane or a placebo for 5 years. The goal of the study was to find out whether exemestane can prevent breast cancer more effectively and with fewer side effects than tamoxifen (Nolvadex, Tamofen) and raloxifene (Evista) in healthy post-menopausal women with a higher than average risk of developing breast cancer. This study found that exemestane lowered the risk of developing breast cancer in these women by two-thirds. However, exemestane only reduced the occurrence of estrogen receptor-positive breast cancer and it caused side effects, such as hot flashes, vaginal dryness and joint and muscle pain in many of the women in the study (New England Journal of Medicine, PMID* 21639806).
- The International Breast Cancer Intervention Study (IBIS-II) is a breast cancer prevention trial that is very similar to the ExCel research study. IBIS-II is testing anastrozole (Arimidex), which is an aromatase inhibitor. This study will close in December 2011.
- Some studies have shown that soy products may reduce the risk of breast cancer. These studies looked at countries where diets are high in soy products (Breast Cancer Research and Treatment, PMID 21113655; European Journal of Clinical Nutrition, PMID 20571498; Journal of Epidemiology, PMID 20173308). Soy contains phytochemicals (active chemical compounds in plants that have effects that promote health). These phytochemicals, called phytoestrogens, have similar effects as estrogen and so block the effects of estrogen in the body. However, women in the studies took in different amounts and types of soy products, so the role of soy products and their components (such as phytoestrogens) in reducing the risk of breast cancer needs further study.
- Studies ofstatins (drugs used to lower cholesterol) and breast cancer risk have had mixed results. Some studies report a decrease in risk and others report an increase in risk. Two studies have reported no association between statin use and breast cancer risk. Further research is needed to understand if there is a link between breast cancer and statins (Cancer Investigation, PMID 21936625; Journal of the National Cancer Institute, PMID 21813413; Cancer Epidemiology, Biomarkers and Prevention,PMID 20729289).
- Researchers have found that aspirin may play a role in lowering the risk of several types of cancer. A large study (called a meta-analysis) found that regular use of aspirin was associated with a reduced risk of breast cancer. More research is needed before a recommendation can be made for the use of aspirin in cancer prevention (Lancet Oncology, PMID 22440112).
- Researchers have found that vitamin D intake may lower the risk of breast cancer (Anticancer Research, PMID 21868542; Journal of Epidemiology, PMID 21160130; Breast Cancer Research and Treatment, PMID 19851861). A Canadian study found that vitamin D supplements, not vitamin D-enriched foods, were associated with a lower risk of breast cancer (American Journal of Clinical Nutrition, PMID 20392891). Another study suggested that a high intake of vitamin D may be associated only with a lower risk of developing premenopausal breast cancer (Cancer Science, PMID 20151981). More research is needed to further our understanding of how vitamin D could potentially lower the risk of breast cancer.
- Lignans are a type of phytoestrogen (a substance that has an effect similar to estrogen). They are commonly found in flaxseed and other seeds, grains, fruits and vegetables. Studies have found that a high intake of lignans was associated with a reduced risk of breast cancer in post-menopausal women (International Journal of Cancer, PMID 21544804; American Journal of Clinical Nutrition, PMID 20463043).
- It is not clear what effect lignans may have on women who have breast cancer. Until more is known, women with breast cancer should talk to their healthcare team if they have questions about eating flaxseed or flax-based foods and the amount that may be consumed.
- The VITamins And Lifestyle (VITAL) Cohort is a group of post-menopausal women in Washington State who were studied to see what type of vitamins and supplements they used. In this group of women, fish oil supplements were found to be associated with a reduced risk of ductal breast cancer. Further research is needed to know whether fish oil has a chemoprotective effect on the development of breast cancer (Cancer Epidemiology, Biomarkers and Prevention, PMID 20615886).
- Celiac disease (sprue) damages the small intestine and interferes with the absorption of nutrients from food. People with celiac disease have sensitivity to gluten – a protein found in grains such as wheat, rye and barley. A study has found that women with celiac disease have a lowered risk of developing breast cancer. Researchers are looking into why women with celiac disease may be less likely to develop breast (International Journal of Cancer, PMID 21953605).
Screening
Researchers are working to improve screening techniques for breast cancer so that it can be found early, before signs and symptoms are noticed.
Noteworthy research includes:
- Magnetic resonance imaging (MRI), used in combination with mammography, may play an important role in screening women who at a higher risk of developing breast cancer. MRI may find more cancers at an earlier stage and in women whose cancer may not be easily detected by mammograms. Data from studies suggest that MRI may be most useful in screening women with a BRCA1 or BRCA2 gene mutation or high-risk family history of breast cancer (Cancer, PMID 21935911; Preventive Medicine, PMID 21745498; Academic Radiology, PMID 19000876). However, MRI has many more false-positive results than mammography alone, so MRI is not a useful way to screen women who are not at very high risk.
- Researchers are trying to find out if using ultrasound in addition to mammography will be a more effective way to screen women for breast cancer. Studies have found that these 2 tests, compared with mammography alone, helped doctors to find more breast cancers in high-risk women, particularly those with dense breasts. However, using ultrasound and mammography to screen for breast cancer may result in more false-positive results than screening with mammography alone (European Journal of Cancer, PMID 21211962; European Radiology, PMID 19727744; JAMA, PMID 18477782).
- Researchers are studying a technique called computer-aided detection (CAD) to see if it is helpful at finding breast cancer in screening mammograms. CAD computer software looks for tissue changes in a mammogram that may indicate the presence of breast cancer. By using CAD, doctors hope to lessen the impact of human error that is associated with reading mammograms. (For example, some radiologists may find slight changes in mammograms that are potentially cancer, while others may not.) More research is needed to see if CAD improves breast cancer detection by mammography (Journal of the National Cancer Institute, PMID 21795668; Radiology, PMID 20656831; Archives of Gynecology and Obstetrics, PMID 19023581; New England Journal of Medicine, PMID 18832239).
- Breast tomosynthesis (BT) is an imaging test similar to mammography. A woman lies face down with her breast hanging down through a hole in the table. An x-ray machine rotates around the breast and takes 3-dimensional (3-D) images (slices), which are sent to a computer. The thin, sliced images help to prevent tissue overlap that is seen on conventional mammograms. The images can be combined to produce 3-D pictures that give a more detailed view of a particular area of the breast. BT may allow doctors to see smaller abnormal areas in the breast that may otherwise be hidden on a conventional mammogram. This is of particular importance in women with dense breasts. BT has been shown to be more sensitive than digital mammography in detecting breast cancer and assessing tumour size, but it is still considered an experimental technique (Acta Radiologica, PMID 21498340, PMID 20105090; European Radiology, PMID 18641998).
- Breast-specific gamma imaging is a type of nuclear medicine imaging test used to detect abnormal areas, including tumours, in the breast. It uses a radiopharmaceutical that can be taken up by breast tissue. The radiopharmaceutical will be found in higher amounts in a tumour than in normal areas of the breast. A special camera called a gamma camera then tracks the radiopharmaceutical as it moves through the breast. The recordings are fed into a computer, which puts them together to make a picture. Breast-specific gamma imaging is being studied as a diagnostic test for breast cancer. There is some evidence that it may be particularly useful in women with dense breasts (Annals of Nuclear Medicine, PMID 22006539; Annals of Surgical Oncology, PMID 21739318; British Journal of Radiology, PMID 21712429).
Diagnosis
A key area of research activity involves developing better ways to diagnose and stage breast cancer.
Noteworthy research includes:
- Positron emission tomography (PET) scans are not routinely used to diagnose breast cancer. They are used occasionally to help stage breast cancer, to monitor a person’s response to treatment or help detect recurrence. When PET is used, it is usually done in combination with computed tomography (PET/CT) (BMC Cancer, PMID 22011459; European Journal of Surgical Oncology, PMID 21937190; Cancer, PMID 21472709; Journal of Clinical Oncology, PMID 19075273). PET/CT may also be a useful tool for staging breast cancer, including inflammatory breast cancer (Cancer, PMID 19645022; European Journal of Radiology, PMID 18814983).
- Positron emission mammography (PEM) is a specialized type of PET scan that is being studied as a diagnostic tool for breast cancer. Like PET, PEM uses a radiopharmaceutical (a drug that contains a radioactive substance) made up of a radioactive isotope attached to a natural body compound, usually glucose. The radiopharmaceutical concentrates in the breast. The exam is done similar to mammography. The PEM detectors are attached to plates that compress the woman’s breast. PEM has been shown to be as effective as magnetic resonance imaging (MRI) in planning treatment for women with breast cancer (Radiology, PMID 21076089; European Journal of Nuclear Medicine and Molecular Imaging, PMID 20871992).
- It remains unclear if MRI will have a role in planning treatment in women with breast cancer. A recent article reported that MRI can help plan treatment before surgery because it can find hidden areas of breast cancer that were not identified with conventional imaging. MRI, however, can sometimes change the treatment plan, resulting in unnecessary radical surgery (such as mastectomy) when breast-conserving approaches (such as lumpectomy followed by radiation) could have been offered. More research is needed to determine the role that MRI may play in planning treatment in women with breast cancer (CA: A Cancer Journal for Clinicians, PMID 19679690).
- There is some evidence that computer-aided detection (CAD), in addition to screening, may also be helpful as a diagnostic tool for breast cancer (European Journal of Radiology, PMID 21345631).
Prognostic and predictive factors
Prognostic and predictive factors that may help determine the outcome of the disease are being studied in breast cancer. A prognostic factor is an aspect of the cancer or a characteristic of the person that the doctor will consider when making a prognosis. A predictive factor influences how a cancer will respond to a certain treatment. Prognostic and predictive factors are often discussed together and they both play a part in deciding on a treatment plan and a prognosis.
Noteworthy research includes:
- New molecular methods for classifying breast cancer have been developed based on gene expression profiling using DNA microarray studies. Microarrays allow scientists to quickly and accurately analyze many genes at one time using specialized equipment. Recent studies have used gene expression profiling to identify distinct types of breast cancer with distinct clinical and prognostic factors (Breast Cancer Research, PMID 21787441, PMID 20576095; Cancer Treatment Reviews, PMID 21277684; International Journal of Cancer,PMID 19101988).
- The 21-gene breast cancer assay is a laboratory test that uses gene expression profiling to determine which hormone receptor–positive breast cancers are likely to spread (metastasize) or come back (recur). This test can also be used to help find out which women are most likely to benefit from adjuvant chemotherapy in addition to hormonal therapy. Oncotype DX is an example of a 21-gene breast cancer assay (test). This test determines a recurrence score between 0 and 100 from a breast tumour sample. A recurrence score of 17 and under indicates low risk of recurrence and no benefit from adjuvant chemotherapy. A score between 18 and 30 indicates intermediate risk of recurrence and a small benefit from adjuvant chemotherapy. A score of 31 and above indicates a moderately high risk of recurrence and significant benefit from adjuvant chemotherapy. Some provinces will fund this test if it is specially requested by the oncologist. Other prognostic laboratory tests using gene expression profiling include MammaPrint and H/I. Researchers are currently looking at the clinical potential of these tests (Oncologist, PMID 22016474; Journal of Clinical Oncology, PMID 21990413; Annals of Surgical Oncology, PMID 21537874; Pathology, PMID 21233672; Lancet Oncology, PMID 20005174; Journal of Surgical Oncology, PMID 19204954).
- A large study found that men with breast cancer tend to develop the disease at an older age than women. On average, men were about 70 years old before they developed the disease. By comparison, the average age for women was about 62 years. At the time of diagnosis, men had more advanced disease compared to women in the study. However, men had a more favourable prognosis compared to women (Journal of Clinical Oncology, PMID 21969512).
Treatment
Researchers are looking for new ways to improve the treatment of breast cancer. Advances in cancer treatment and new ways to manage the side effects related to treatment have improved the outlook and quality of life for many people with cancer.
Noteworthy research includes:
Surgery
Researchers are studying new surgical techniques that could potentially improve the cosmetic outcome of breast surgery.
- Advances in surgical techniques have improved satisfaction and the cosmetic outcome for women undergoing breast reconstruction following mastectomy. Researchers have shown that total skin-sparing mastectomy (TSSM) is as effective a treatment as conventional mastectomy procedures. Most of the skin covering the breast tissue remains following TSSM, but the nipple and areola may be removed. Nipple-sparing mastectomy, which is a type of TSSM that tries to preserve the nipple and areola, is also being investigated. This surgical technique removes the nipple and areola, which are then examined by a pathologist. If no cancer is found, they are reattached during reconstruction. This procedure tends to be more challenging because the blood supply to the nipple and areola must be reconnected or the tissue will die. Not all women are candidates for these new surgical techniques. These surgical techniques may be attractive to women who are recommended to undergo prophylactic mastectomy due to an increased risk of breast cancer (Annals of Surgical Oncology, PMID 21979111, PMID 21847697; Surgical Oncology Clinics of North America, PMID 20620927; BMC Cancer, PMID 20429922; Annals of Surgery, PMID 20134317, PMID 19106672; British Journal of Surgery, PMID 20101646).
- Oncoplastic surgery is a specialized type of surgery that uses both cancer surgery and plastic surgery techniques. Oncoplastic surgery is being explored in women whose breast appearance may be greatly altered by breast-conserving surgery. The breast is reshaped at the time of the cancer surgery. Sometimes the opposite breast may need to be reduced to match the size of the breast that had cancer. A study reported that the rates of recurrence and survival with oncoplastic surgery were similar to those of breast-conserving techniques (Breast, PMID 22015301; Annals of Plastic Surgery, PMID 21862918; Plastic and Reconstructive Surgery, PMID 20124831).
- Autologous fat transfer is a technique that moves fat from one area of the body to another. It may be done during breast reconstruction. It can be done simply and safely and has shown improvements in the results of reconstructive breast surgery (Annals of Plastic Surgery, PMID 21451387; Breast, PMID 20347309; Journal of Plastic, Reconstructive and Aesthetic Surgery, PMID 18848513).
Radiation therapy
Researchers are looking at various radiation therapy techniques to treat women with breast cancer. These radiation techniques have the advantage of being more convenient because people may not have to travel or be away from home as often as with conventional external beam radiation treatment.
- Doctors are studying whether giving radiation treatment using different schedules is more effective at destroying cancer cells. They are experimenting with hypofractionation radiation schedules, in which a higher overall dose of radiation is given in fewer treatments over a shorter period of time. Studies have shown that hypofractionation is just as effective at treating breast cancer as the standard radiation treatment schedule (Seminars in Radiation Oncology,PMID 21134655; Cancer, PMID 20803608; New England Journal of Medicine, PMID 20147717).
- Accelerated partial breast irradiation(APBI) is radiation treatment in which a higher overall dose of radiation is given in fewer treatments over a shorter period of time. APBI is given to women who have had a lumpectomy and require adjuvant radiation therapy. Radiation is only given to the area of the breast that contained cancer because, in most cases, any cancer cells left behind are usually found within the area of the lumpectomy. Researchers have shown that APBI is as effective at preventing recurrence in women with early stage breast cancer as conventional whole-breast irradiation (Cancer, PMID 21381007; Seminars in Radiation Oncology,PMID 21134655; Radiation Oncology, PMID 20920346; International Journal of Radiation Oncology, Biology, Physics, PMID 20800374, PMID 20472364, PMID 19058921; Annals of Surgical Oncology, PMID 20737219; Radiation Oncology, PMID 20565899). APBI can be delivered in several ways, including:
- brachytherapy
- conformal radiation therapy
- intraoperative radiation therapy (IORT)
- IORT is a type of APBI in which external beam radiation therapy is directed at the tumour during surgery. The surgeon removes as much of the tumour as possible. Normal tissues are moved out of the radiation beam to protect them. The radiation is aimed directly at the tumour bed. This allows a high, single dose of radiation to be delivered to the area of the breast that contained cancer (Cancer Letters, PMID 21930343; Lancet, PMID 20570343). Researchers are also studying brachytherapy techniques as a way to deliver IORT. Doctors put an applicator inside the breast after the tumour has been removed. A radioactive source is then put inside the applicator to deliver radiation. This technique is called targeted intraoperative radiation therapy (International Journal of Radiation Oncology, Biology, Physics, PMID 20951505; Lancet, PMID 20570343).
- A phase III study found that radiation therapy with accelerated partial breast irradiation(APBI) plus intensity-modulated radiotherapy (IMRT) was safe and was associated with low toxicity when used in women with early stage breast cancer (International Journal of Radiation Oncology, Biology, Physics,PMID 19700248). IMRT has also shown good results when used after breast-conserving surgery (International Journal of Radiation Oncology, Biology, Physics, PMID 21345620; Seminars in Radiation Oncology, PMID 21134654; Breast Journal, PMID 19624420).
Chemotherapy, hormonal therapy and biological therapy
New chemotherapy, hormonal therapy and biological therapy drugs continue to improve the treatment and control of breast cancer. The following are some of the latest research trends in the treatment of breast cancer with drugs.
- Epothilones are a new class of drug that can prevent cancer cells from dividing. Ixabepilone (Ixempra), an epothilone, is showing promise in treating metastatic breast cancer that is resistant to other types of chemotherapy. Ixabepilone may be used alone or in combination with capecitabine (Xeloda) for women who were previously treated with anthracycline-based or taxane-based chemotherapy. Triple negative breast cancers (estrogen-receptor negative, progesterone-receptor negative and HER2-negative) appear to also respond to ixabepilone. This is an exciting result because these types of tumours generally have limited treatment options (Clinical Breast Cancer, PMID 21665133; Breast Cancer Research and Treatment,PMID 21128114, PMID 20229176; Journal of Clinical Oncology, PMID 20530276; Future Oncology, PMID 20146579).
- A phase III study looked at women with metastatic breast cancer that did not respond to 2–5 previous chemotherapy treatments. Eribulin mesylate (E7389) is a non-taxane chemotherapy drug that binds to very small tubes (microtubules) in the cell and disrupts cell division. Women given eribulin mesylate survived an average of 2.5 months longer than women who were given other chemotherapy drugs (Lancet, PMID 21376385). This drug is available in Canada for compassionate use or through a clinical trial.
- Trastuzumab (Herceptin) is a biological therapy that is commonly given to women with HER2-positive breast cancer. Trastuzumab emtansine (trastuzumab-DM1) is made up of the drugs trastuzumab and mertansine, a newly developed anti-cancer (cytotoxic) drug. Trastuzumab emtansine is being studied in women with metastatic HER2-positive breast cancer. Results from early studies have been promising. There are several ongoing phase III trials that are testing trastuzumab emtansine in women with metastatic HER2-positive breast cancer (Expert Opinion on Biological Therapy, PMID 21506905; Current Opinion in Molecular Therapeutics, PMID 20521224). The combination of trastuzumab with other agents used to treat HER2-positive breast cancer, such as lapatinib (Tykerb), nilotinib (Tasigna) and pertuzumab (Omnitarg), is also showing promise in treating HER2-positive breast cancers.
- Bisphosphonates may be given to women with breast cancer that has spread to the bones. These drugs help strengthen the bones and prevent them from breaking down. There is some evidence that zoledronic acid (Zometa, Aclasta), a type of bisphosphonate, may also be effective at treating breast cancer when given with adjuvant hormonal therapy. However, not all studies have reported positive results. More research is needed to see if bisphosphonates may help to prolong survival in premenopausal women with early-stage breast cancer (New England Journal of Medicine, PMID 21995387; Lancet Oncology, PMID 21641868; New England Journal of Medicine, PMID 19213681).
- A Canadian study has found that women who take both tamoxifen (Nolvadex, Tamofen) for breast cancer and paroxetine (Paxil), a drug commonly prescribed for depression, have an increased risk of death from breast cancer. It is believed that paroxetine interferes with the body’s ability to convert tamoxifen to its active form, making it ineffective in treating breast cancer. The risk of death appears to increase the longer both drugs are used over the same period of time. No increase in the risk of death from breast cancer was found with the other antidepressant drugs that were studied (BMJ, PMID 20142325). Women with breast cancer who may receive treatment with tamoxifen should speak to their oncologists if they are taking paroxetine.
- A group of drugs called poly(ADP-ribose) polymerases(PARP inhibitors) affect certain tumour cells so they cannot repair damage to DNA. These drugs appear to have little effect on normal cells. They may be particularly active if given with chemotherapy that damages DNA. PARP inhibitors are showing promise in early studies for the treatment of epithelial ovarian cancer in women who carry a BRCA gene mutation. They are also being studied in women with breast cancer who carry a BRCA gene mutation (Oncology, PMID 22106552; Expert Review of Anticancer Therapy, PMID 21916578).
- Mammalian target of rapamycin (mTOR) inhibitors are drugs that stop cell growth. Researchers are studying the mTOR inhibitor everolimus(Afinitor) in women with post-menopausal hormone receptor–positive advanced breast cancer. Results of a phase III trial showed that everolimus given with exemestane (Aromasin) (an aromatase inhibitor) improved progression-free survival in women with hormone receptor–positive advanced breast cancer who were previously treated with aromatase inhibitors (New England Journal of Medicine, PMID 22149876). Researchers have not yet found if everolimus prolongs overall survival. It can also cause unwanted side effects. More research is needed to find out what role everolimus may play in the treatment of women with breast cancer.
Supportive care
Living with cancer can be challenging in many different ways. Supportive care can help people cope with cancer, its treatment and possible side effects.
Noteworthy research includes:
- Preserving their fertility is a concern for many premenopausal women with breast cancer. Chemotherapy can damage the ovaries. Women who take tamoxifen, a type of hormonal therapy, are advised not to become pregnant because this drug may cause birth defects. Tamoxifen may be taken for up to 5 years, so women may no longer be fertile by the time the drug is stopped. The following describes research into preserving fertility in women with breast cancer:
- Women with breast cancer have the option to freeze and store embryos before they begin adjuvant treatment for breast cancer. Researchers have reported a high success rate with freezing eggs, which can then be thawed and fertilized with sperm from a partner or donor at a later date. Freezing ovarian tissue, which can be implanted in the body after treatment is completed, may also be an option. This technique is considered highly experimental as very few successful pregnancies have been reported to date in women who have had this procedure (European Journal of Obstetrics & Gynecology and Reproductive Biology, PMID 22137982; Current Opinion in Obstetrics & Gynecology, PMID 19125006).
- A study found that early referral to a reproductive specialist is helpful to women who will undergo adjuvant treatment for breast cancer and who still wish to have children. Having the referral before breast surgery means that the process to freeze eggs or embryos can be started earlier. When the process to freeze either eggs or embryos is started earlier, more eggs or embryos can be frozen to increase the chances of preserving fertility. There is also less risk of a harmful delay before starting adjuvant therapy (Journal of Clinical Oncology, PMID 20876425).
- Ovarian ablation with luteinizing hormone–releasing hormone (LHRH) agonists such as goserelin (Zoladex), leuprolide (Lupron, Lupron Depot, Eligard) or triptorelin (Trelstar) may sometimes be used to treat women with hormone receptor–positive breast cancer. Recently, LHRH agonists have been used in premenopausal women with breast cancer who are undergoing chemotherapy. LHRH agonists work by “shutting off” the ovaries while chemotherapy is given. The hope is that ovarian function will resume once these drugs and the chemotherapy are stopped, which may allow women to maintain their fertility. Goserelin does not appear to protect ovarian function if given in combination with tamoxifen (JAMA, PMID 21771987; Breast Cancer Research and Treatment, PMID 19153828).
- Contrary to previous beliefs, recent research has found that having a baby after all treatment for breast cancer is complete is safe. It but may also be linked to a lower chance of recurrence and lower risk of death due to breast cancer (Archives of Gynecology and Obstetrics, PMID 21221981; European Journal of Cancer, PMID 20943370).
- Denosumab (Xgeva) is a type of monoclonal antibody. Researchers are testing this drug to see if it can strengthen bones and prevent osteoporosis in women with breast cancer that has spread to the bone. When given every 6 months, denosumab increases bone density in women (Expert Opinion on Biological Therapy, PMID 19653867; Breast Cancer Research and Treatment, PMID 19308727). Other studies have found that women with breast cancer had less bone pain, fewer bone fractures and a better quality of life when given denosumab compared to those who were given zoledronic acid (Journal of Clinical Oncology, PMID 21060033; ASCO**, Abstract 1024, Abstract 1025).
*PMID is the National Library of Medicine PubMed abstract identity number.
**ASCO is the American Society of Clinical Oncology.
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