Risk Management
Close surveillance for breast cancer
Overview
Close surveillance or screening for cancer routinely uses tests to try to catch cancer in its early stages, when it is most treatable. Surveillance doesn’t prevent cancer. However, early detection improves a person’s chance of surviving their cancer. Studies of breast cancer screening tools for high-risk women, some including women with BRCA mutations, found certain screening more likely to detect cancer. Whether close surveillance will lower the death rate from breast cancer in high-risk women is unknown. Nevertheless, based on these studies, recommendations for breast cancer screening in the high-risk population differ from recommendations for the general population.
In women with BRCA mutations or other hereditary risk factors, breast cancer tends to occur at a younger age, and the lifetime risk for cancer is higher than the general population. Therefore, screening tests that might not be appropriate for women of average risk may be recommended for those in the high-risk category. As surveillance for breast cancer in high-risk women is further researched, screening recommendations will likely change. For the above reasons, it is important to consult with health care experts who are familiar with the standards of care and risk management in high-risk women. Further, it is important to understand that sweeping recommendations regarding cancer surveillance may not apply to women with increased risk for cancer.
The National Comprehensive Cancer Network (NCCN) is a consortium of cancer centers with experts in management of hereditary cancer.In general, NCCN guidelines dictate the standard of care for cancer surveillance in high-risk patients. These risk management guidelines are updated annually based on the latest research. Current NCCN guidelines for surveillance of high risk women include:
- Breast self-exam training and regular monthly BSE starting at age 18
- Clinical breast exam, semiannually, starting at age 25
- Annual mammogram and/or MRI starting at age 25 or individualized based on earliest age of onset in family
Screening terminology
Scientists use the following criteria when considering the utility of a screening test:
- Sensitivity (true positives):
the probability of a positive test among those who have the disease. If two women in a group of 100 have cancer, for example, a highly sensitive test would find positive results in both women. - Specificity (true negatives):
the probability of a negative test among those who do not have the disease . If only two women in the group of 100 have cancer, but 10 falsely test positive, the test is not very specific.
The ideal test is both sensitive and specific. If someone tests positive, they likely have the disease. If they test negative they likely don’t. It is difficult to develop a test that is highly sensitive and highly specific. Usually one quality is compromised at the expense of another.
Breast Exams
Breast exams refer to the routine examination of breast tissue to look for lumps or other changes that might indicate cancer. There are two categories of breast exams: Breast Self Exam (BSE) and Clinical Breast Exam (CBE). BSE refers to self-examination of the breasts on a regular (usually monthly) basis, using a systematic method to examine all the breast tissue. Studies have looked at whether Breast Self Exam lowers the risk of death by breast cancer. One large randomized study involving 266,000 women found no reduction in breast cancer death in a 10-year period in women who were taught to perform monthly breast exams. The same research discovered women who practiced regular SBE had more biopsies and procedures for benign lumps than women who did not. Based on this data, some expert panels, including NCCN, do not recommend BSE as a standard recommendation for breast cancer screening for women in the general population. There has been no similar study on BSE in high-risk women. Current NCCN recommendations for women with hereditary breast cancer risk include BSE training and monthly BSE in women beginning at age 18.
CBE refers to examination of a patient’s breasts by a health care professional to detect lumps or other abnormalities. In one study CBE was combined with other screening tools to detect breast cancer in BRCA carriers. Used alone, CBE was found to be an ineffective method of finding cancers. However, when combined with mammography, CBE improved the chances of finding cancer. The NCCN recommends a twice-yearly clinical breast exam for high-risk women beginning at age 25.
Mammograms
Mammograms are x-rays that provide an image of the internal breast structure. Screening mammograms refer to x-rays of the breasts of healthy women in order to find abnormalities. Mammograms are considered the standard screening tool for finding breast cancer in the general population of women after age 40. However, mammography is not perfect, nor is it highly sensitive— the technology misses some breast cancers (false negatives), especially in younger women whose denser breasts. Many changes (false positives) detected by mammograms require a biopsy and turn out to be non cancerous.
Most studies of mammograms in high-risk women or BRCA carriers involved comparison with other imaging techniques such as Magnetic Resonance Imaging (MRI). An article addressing MRI and mammograms in BRCA carriers pointed out that while mammograms had a low sensitivity of 36% (meaning the technology failed to identify many cancers), they had a specificity of 99.8% (meaning there were few false positives and most of the abnormalities identified by mammograms as cancer turned out to be cancer). In another study comparing MRI and mammograms in high-risk women (including but not exclusive to BRCA positive women), MRI generally found more cancers than mammograms, but missed some cancers found by mammography. Although imperfect and not as sensitive as MRI, mammograms are readily available. For these reason, annual mammograms beginning at age 25 are still recommended for high-risk women.
A recent publication explored the theoretical benefits and risks of mammography in young, high-risk women younger than 30. The study affirms the benefits of mammograms for BRCA carriers over age 30, but raises questions about relative risks versus benefits for younger women. One of the researchers, reported that results of this exercise raise questions about the practice of recommending mammograms from age 25, but do not provide enough evidence to change protocols.
Magnetic Resonance Imaging (MRI)
Breast MRI is an imaging method using magnetic fields rather than x-rays to produce a detailed picture of the breasts.
One study compared mammography and MRI in women with risk factors for hereditary cancer. The majority of women in this research did not have BRCA mutations .Mammography missed two-thirds (66%) of the breast cancers identified by MRI, but found 61% of cancers missed by MRI. Cancers found in women receiving MRI were more likely to be earlier stage and less likely to involve lymph nodes than cancers detected by mammography.
Another study compared MRI, mammograms and ultrasound in 236 women aged 25 to 65 years with BRCA1 or BRCA2 mutations. Even though MRI was generally more sensitive than mammograms, mammography still found cancers MRI failed to detect. However, MRI may be particularly good at finding cancers in premenopausal, high-risk women, a group with typically dense breasts that don’t image well by mammogram. In a study of high-risk women age 35-49, adding MRI to mammography increased the sensitivity from 40% to 94% for finding cancer in high-risk women. This study found that MRI was particularly sensitive in finding breast cancer in women with BRCA 1 mutations.
MRI has some drawbacks. It is less specific than some other screening tests for breast cancer. Although MRI is sensitive and may pick up an abnormality missed by other techniques, there is a greater chance for the abnormality to be benign. Unfortunately, a biopsy is required to determine if a change is cancerous. Women who undergo breast MRI are more likely to have biopsies for changes that are not cancerous. Although this lower specificity may not be acceptable for screening of women of average risk, many experts believe the benefit of MRI outweighs the risk for women with hereditary risk for breast cancer.
Because MRI is still a relatively expensive test, not all insurance companies will pay for it, even in women with a demonstrated BRCA mutation. Further, not all facilities have MRIs specifically made for imaging the breast or radiologists capable of interpreting breast MRI results. And some facilities are not set up for MRI-guided biopsy. That means even if the facility has a breast MRI, it may not have the capability to biopsy an MRI-detected abnormality not seen by mammography or ultrasound. For these reasons, MRI is not yet universally considered standard of care for BRCA carriers, although NCCN and the American Cancer Society have both included MRI in their recommendations for screening of high-risk women.
Additional studies to further determine the benefits of MRI in high-risk women are ongoing. To learn more about breast surveillance research, visit our clinical trials section.
Ultrasound
Breast ultrasound (also called sonogram) is an imaging method using sound waves to look at the internal structure of breasts. Ultrasound is particularly sensitive at distinguishing fluid-filled cysts from solid masses. Therefore, in women of average risk, ultrasound is not used as a screening tool for breast cancer, but is used as a diagnostic tool to get a better view of abnormalities found through examination or mammogram. Studies have looked at ultrasound as a screening tool for breast cancer in high-risk women. One study compared mammograms, MRI and ultrasound for screening in women with BRCA mutations. In this study, ultrasound found only 33% of the cancers found in the study compared with 77% found by MRI. Research to further determine the benefits of ultrasound in high-risk women are ongoing. Currently there are no NCCN recommendations for breast screening using ultrasound. To learn more about research on breast surveillance, visit our clinical trials section.
Ductal lavage
Ductal lavage is a non-surgical screening tool to detect early abnormalities in the breast. A slim tube inserted through the nipple washes fluid into the milk ducts and collect cells. Sometimes ductal lavage can detect very early breast changes such as atypia, before they can be identified by other means. One small study of MRI and ductal lavage in high-risk women, including women with BRCA mutations, found abnormal cells in the fluid from 7 women, including one woman who had a normal MRI and mammogram. A recent study showed ductal lavage often didn't produce enough fluid and cells for analysis. And a third study showed results from ductal lavage were not always reproducible when abnormal cells were found in the fluid. In this study ductal lavage was neither highly specific (has many false positives), nor highly sensitive (has many false negatives). Currently ductal lavage is not routinely recommended for screening in high-risk women. However, research to further determine the benefits of ductal lavage in high-risk women are ongoing. To learn more about breast surveillance research, visit our clinical trials section.
Breast screening in men
Men with BRCA mutations have a lifetime risk of up to 7% for breast cancer; higher than men in the general population but much lower than high-risk women. Male breast cancer is uncommon, even in men with BRCA mutations. Therefore, there is very little research on breast cancer detection in high-risk men. Current NCCN recommendations for breast cancer surveillance in male BRCA carriers include:
- Breast self-exam training and regular monthly practice
- Annual clinical breast exam
- Consider baseline mammogram,
- annual mammogram if gynecomastia (breast enlargement) or breast density on baseline study
Other websites
Breast
Self Examination: Your Key to Better Breast Health (pdf)
From the Y-Me National Breast Cancer Organization.
Ductal
Lavage
This minimally invasive procedure can be used in conjunction with other surveillance
in high-risk women. Studies on women who are at high risk for developing breast
cancer have shown that this method can detect pre-cancerous or cancerous changes
that were missed on mammography. The website contains good information on the
ductal lavage procedure.
Magnetic Resonance Breast
Imagine
An overview of MRI, including photographs of the machine and an explanation
of the procedure’s benefits and limitations.
National
Comprehensive Cancer Network
Comprehensive Cancer Network is a consortium of experts in the field of oncology.
The NCCN publishes a consensus guide for breast cancer high-risk women with
input from the top geneticists and experts in high-risk management.
Clinical trials
ClinicalTrials.gov
This
site, produced by the U.S. National Library of Medicine (NLM), provides patients,
family members, and members of the public easy and free access to information
on clinical studies for a wide range of diseases and conditions.
Nipple Aspiration, Ductal Lavage, and Duct Endoscopy in Screening Women at Moderate-to-High Risk of Developing Breast Cancer
Note: this study is only enrolling women in the United Kingdom.
Further reading - articles (advanced reading)
Estimated risk of
radiation-induced breast cancer from mammographic screening for young BRCA mutation carriers
Amy Berrington de Gonzalez, Christine D. Berg, Kala Visvanathan, Mark Robson. Journal of the National Cancer Institute. Vol. 101, Number 3, p. 205 - 209.
Oral
contraceptive use and risk of early-onset breast cancer in carriers and
noncarriers of BRCA1 and BRCA2 mutations
Roger L. Milne, Julia A. Knight,
Esther M. John, Gillian S. Dite, Ronald Balbuena, Argyrios Ziogas, Irene
L. Andrulis, Dee W. West, Frederick P. Li, Melissa C. Southey, Graham G.
Giles, Margaret R.E. McCredie, John L. Hopper and Alice S. Whittemore for
the Breast Cancer Family Registry. Cancer Epidemiology
Biomarkers & Prevention.
Vol. 14, Number 2, p. 350-356, February 2005.
Oral
contraceptive use and ovarian cancer risk among carriers of BRCA1 or BRCA2
mutations
A S Whittemore, R R Balise, P D P Pharoah, R A DiCioccio,
Kathleen Cuningham Foundation Consortium for Research into Familial Breast
Cancer (kConFab), I Oakley-Girvan, S J Ramus, M Daly, M B Usinowicz, K
Garlinghouse-Jones, B A J Ponder, S Buys, R Senie, I Andrulis, E John,
J L Hopper and M S Piver. British Journal of
Cancer. Volume 91, Number
11, p. 1911-1915, November 2004.
Oral
contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation
carriers
Steven A. Narod, Marie-Pierre Dubé, Jan Klijn, Jan
Lubinski, Henry T. Lynch, Parviz Ghadirian, Diane Provencher, Ketil Heimdal,
Pal Moller, Mark Robson, Kenneth Offit, Claudine Isaacs, Barbara Weber,
Eitan Friedman, Ruth Gershoni-Baruch, Gad Rennert, Barbara Pasini, Theresa
Wagner, Mary Daly, Judy E. Garber, Susan L. Neuhausen, Peter Ainsworth,
Hakan Olsson, Gareth Evans, Michael Osborne, Fergus Couch, William D. Foulkes,
Ellen Warner, Charmaine Kim-Sing, Olufunmilayo Olopade, Nadine Tung, Howard
M. Saal, Jeffrey Weitzel, Sofia Merajver, Marion Gauthier-Villars, Helena
Jernstrom, Ping Sun, Jean-Sebastien Brunet. Journal
of the National Cancer Institute. Volume 94, Number 23: p. 1773-1779, December 2002.
Aspirin,
other NSAIDs, and ovarian cancer risk
Kathleen M. Fairfield, David
J. Hunter, Charles S. Fuchs, Graham A. Colditz, and Susan E. Hankinson.
Cancer Causes and Control. Volume 13, Number 6: p. 535-542, August 2002.
Effect of fenretinide
on ovarian carcinoma occurrence
Giuseppe De Palo, Luigi Mariani, Tiziana
Camerini, Ettore Marubini, Franca Formelli, Barbara Pasini, Andrea Decensi
and Umberto Veronesi. Gynecologic Oncology. Volume 86, Issue 1: p 24-27,
July 2002.
Parity,
oral contraceptives, and the risk of ovarian cancer among carriers and
noncarriers of a BRCA1 or BRCA2 mutation
Baruch Modan, Hartge, P.,
Hirsh-Yechezkel, G., Chetrit, A., Lubin, F., Beller, U., Ben-Baruch, G.,
Fishman,A., Menczer, J., Struewing, J., Tucker, M., Ebbers, S., Friedman,
E., Piura, B., Wacholder, S., for the National Israel Ovarian Cancer Study
Group. New England Journal of Medicine.
Volume 345, Number 4: p. 235-240, July 2001.
Oral contraceptives
and the risk of hereditary ovarian cancer
Steven A. Narod, M.D., Harvey
Risch, M.D., Ph.D., Roxana Moslehi, M.Sc., Anne Dørum, M.D., Susan
Neuhausen, Ph.D., Hakan Olsson, M.D., Diane Provencher, M.D., Paolo Radice,
Ph.D., Gareth Evans, M.D., Susan Bishop, M.Sc., Jean-Sébastien Brunet,
M.Sc., Bruce A.J. Ponder, M.D., Ph.D., Jan G.M. Klijn, M.D., for The Hereditary
Ovarian Cancer Clinical Study Group. New England
Journal of Medicine. Volume
339: p. 424-428, August 1998.