Recently, I saw a patient in the clinic with a mammogram of one side of her breast, which was a breast cancer. However, during the preoperative bilateral mammogram, the patient was found to have “bilateral breast cancer”, which means that the opposite side of the breast also had cancerous lesions. It seems necessary to talk about the necessity of bilateral mammogram!
1. Definition: Bilateral breast cancer, in a broad sense, includes bilateral primary breast cancer and bilateral breast cancer secondary to one primary and the other. In clinical practice, bilateral primary breast cancer is usually referred to as bilateral primary breast cancer. The chronological order of onset can be considered as bilateral simultaneous breast cancer and bilateral heterochronic breast cancer. However, it is not possible to determine when the cancer ‘occurred’ in clinical practice, and the time of clinical ‘detection’ of the cancer can only be used instead.
Currently, it is believed that the risk of cancer in the contralateral breast increases by 0.5%-1% per year after unilateral breast cancer surgery, so that after 10 years of follow-up, the risk of cancer in the contralateral side is 5%-10%, which is a fairly high probability. Therefore, if you have a history of breast cancer on one side, you should pay attention to the suspicious lesions on the opposite side of the breast and not to miss the best time for treatment by easily diagnosing them as benign lesions. The median age of onset of bilateral breast cancer is 46.2 years, and the median age of onset is significantly higher in men than in women, and the median age of onset of second cancer is higher than that of first cancer; the premenopausal onset is significantly higher than the postmenopausal onset.
2. Etiology and high-risk factors
(1) Simultaneous existence of susceptibility factors: As a paired organ, the breast is affected by the same quality and quantity of carcinogenic factors, so that cancer occurs successively or simultaneously. High-risk factors, such as early menarche, late age of menopause, no childbirth, late age of first birth, obesity, tobacco and alcohol addiction, are also risk factors for BPBC. Literature from European and American countries reports that people with a history of breast cancer on one side are 4-5 times more likely to develop cancer in the opposite breast than healthy people.
(2) Familial genetic predisposition: It is generally believed to be autosomal dominant genetic inheritance, and this genetic predisposition is the result of the combination of the chromosome group susceptible to cancer and certain exogenous carcinogenic factors. Multifactorial analysis of long-term follow-up results of a group of 3211 cases of bilateral breast cancer showed that family history (p=0.001), invasive lobular carcinoma (p=0.02) were statistically significant, and age of onset (p=0.06) was close to statistical significance.
(3) Histological types and stages of breast cancer
The idea that multicentric carcinoma and lobular carcinoma in situ are risk factors for bilateral breast cancer has been widely recognized. However, recent literature points out that some large-scale clinical trials do not support this view. Our relevant meta-analysis also found that ductal carcinoma accounted for the largest proportion of cases.
(4) Carcinogenic potential of the first primary cancer treatment: Radiation therapy for breast cancer can cause BPBC, as well as cancer of the thyroid and other related sites. Inappropriate application of radiation is a medical carcinogenic factor, and the latency period of carcinogenesis by radiotherapy is generally considered to be about 4 years.
(5) Host susceptibility and decreased immune function: According to some statistics, the risk of cancer patients to develop second primary cancer is 11 times higher than that of normal people to develop first primary cancer, and the probability of developing third primary cancer from double primary cancer is 2.20-10.89 times higher than that of developing second primary cancer from single cancer, which shows that the host susceptibility of cancer patients increases. In addition, the decrease of cancer patients’ own immune function, together with the damage of immune function by treatments such as surgery, radiotherapy and chemotherapy, is also one of the reasons for cancer patients to suffer from cancer repeatedly.
(6) Genetic research: The research of BRCAl/2 was carried out earlier and reported the most, among which most scholars believe that BRCA gene mutation is related to BPBC. p53 gene research has also been very in-depth, the rate of p53 mutation in the first primary cancer and second primary cancer of bilateral heterochronous breast cancer are 44% and 68% respectively, which are significantly higher than unilateral breast cancer.
3.Clinical characteristics
The clinical manifestations of bilateral breast cancer are similar to those of unilateral breast cancer, and the main clinical manifestation is the discovery of painless lumps in the breast at the same time or successively. There are several characteristics as follows.
(1) Age and site of onset: The age of onset of bilateral breast cancer is about 10 years earlier than that of unilateral breast cancer, and its peak is 30-40 years old. A small number of second breast cancers can occur after menopause. The most frequent sites of incidence are outer upper quadrant, accounting for 66.7%, followed by outer lower quadrant and areola area, inner upper quadrant and inner lower quadrant.
(2) Clinical staging: Bilateral breast cancer is often detected when bilateral breast examinations are performed at the onset of one side of the breast. Therefore, the staging of bilateral simultaneous breast cancer is similar to unilateral breast cancer, and bilateral heterochronic breast cancer is often earlier than unilateral breast cancer.
(3) Histological types: The pathological types of bilateral breast cancer are different only 50%-70%, which is not statistically different from unilateral breast cancer. Invasive non-specific carcinoma is the most common type, among which the top 4 are invasive ductal carcinoma (69.4%), medullary carcinoma (5.8%), intraductal carcinoma (5.4%) and invasive lobular carcinoma (4.8%). In the case of BPBC detected by contralateral mastectomy or biopsy of unilateral breast cancer, it is often a non-clinical stage with an increased proportion of lobular carcinoma in situ. More contralateral breast cancers detected by screening are lobular carcinoma and those with negative axillary lymph nodes.
(4) Interval time: From the biological characteristics of tumors, breast cancer takes 2.5-3 years to grow from 1 cancer cell to a tumor of lcm in diameter. If the criteria for defining bilateral breast cancer are too short, it is possible that some of the heterochronous breast cancers are essentially bilateral simultaneous breast cancers. The two are only relative.
(5) Gender and other: BPBC in men is rare and often reported as a case. Among breast cancer with extramammary primary cancer, breast cancer with reproductive system, digestive system or thyroid cancer is more common.
4.Auxiliary examination
Bilateral mammogram, ultrasound and breast MRI are important for the diagnosis of bilateral breast cancer, and if used in combination, they can improve the diagnostic accuracy. Image guided puncture biopsy pathology is the gold standard.
5.Treatment: Comprehensive treatment mainly based on surgery.