Joan (not her real name), a hospital pharmacist, approached her 35th birthday with dread. Few women in her family had managed to live much beyond that age without succumbing to breast cancer. While in her early teens Joan had lost her mother to the dreaded disease that had also killed her grandmother. Joan’s only sister had recently been diagnosed with advanced breast cancer and the doctors all admitted her prognosis was grim.
Joan’s story is not unique. Five to 10 per cent of all breast cancer is caused by an inherited defective gene. Such cancers are termed ‘hereditary breast cancer’. In about half these families a mutation (genetic defect) in a BRCA1 or BRCA2 gene can be found in the relatives with cancer. In the other families the mutation is likely in one or more genes yet to be discovered. Each child of a parent with a BRCA1 or BRCA2 mutation has a 50 per cent chance of inheriting the mutation. Women who inherit such a mutation have up to an 80 per cent lifetime risk of developing breast cancer. To make matters worse, the average age of diagnosis of breast cancer in these women is the mid-forties, 20 years earlier than it is for breast cancer in the general population.
Joan recently learned that she, like her sister, carries a BRCA1 mutation. For women like Joan there are few good options. Some choose prophylactic mastectomy, i.e. surgical removal of their healthy breasts, with or without reconstruction. While such surgery is extremely effective at preventing breast cancer, most women are unwilling to undergo mutilating surgery to prevent a cancer which is often curable, and may never even develop. For these women the only other option is close follow-up with yearly mammograms and frequent breast examinations in the hope that if and when breast cancer occurs it will be found at an early and curable stage.
For Joan, the idea of prophylactic mastectomy was repugnant. But her doctor’s promise that he would keep a close eye on her with mammograms and breast examinations offered her little reassurance. Her sister had found her own cancer only 2 months after a normal mammogram and examination by her doctor. In fact, about half the cancers in BRCA1 and BRCA2 mutation carriers, particularly those that occur in young patients, are missed by mammography. This is because the breasts of young women generally have much more dense glandular and fibrous tissue which can obscure a tumour, than the fatty breasts of older women. For BRCA1 and BRCA2 mutation carriers who have a substantial risk of breast cancer by the age of 25 to 30, a screening modality that can reliably detect breast cancer in younger women is essential.
A multidisciplinary team of researchers at Sunnybrook & Women’s College Health Sciences Centre, led by Dr. Ellen Warner, a medical oncologist, and Dr. Donald Plewes, a medical biophysicist, began a study in November, 1997, to determine whether breast magnetic resonance imaging (MRI) or breast ultrasound might be more effective than mammography for screening these very high risk women. Eligible women are either proven or likely to carry hereditary breast cancer gene mutations and between the ages of 25 and 65. Women with a past history of breast cancer may enroll, provided they have at least one breast which has never been irradiated. Study participants undergo yearly mammography, breast ultrasound and MRI, and 6-monthly clinical breast examination by a study physician or nurse. MRI involves injection of a contrast agent, Gadolinium DTPA, which localizes in areas of the breast with a high concentration of blood vessels. By following the rate at which the contrast agent flows in and out of an area in which it has localized, one can often distinguish the abnormal leaky vessels of tumours from those of benign lesions. Both MRI and ultrasound are much less dependent on breast density than mammography. If there is a suspicious finding on the clinical breast examination, mammogram, ultrasound or MRI (each is rated independently) a biopsy is done, usually with a needle under local anesthetic (core biopsy).
To date 360 women like Joan have enrolled in this study and have undergone at least 1 round of all four screening methods. A total of 17 cancers have been detected in 16 women by screening. Only eight of these cancers were detected by mammography, two by clinical breast examination, and seven by ultrasound. Thirteen of these cancers, however, were detected by MRI. Five of these cancers were only detected by MRI and not by any other method. Two of the four cancers missed by MRI could be seen on MRI in retrospect. Only one cancer so far was picked up by a patient, seven months after normal screening. All but one of these cancers have been early (stage I) with more than an 85 per cent cure rate. Joan now feels much more confident that if she develops breast cancer it will be caught early.
The study, which has been generously funded by the Canadian Breast Cancer Research Initiative, as well as the National Breast Cancer Fund, the U.S. National Cancer Institute and some private donations, will continue to accept new patients at least until July 1, 2002.