1.What is breast cancer?
Breast cancer is a disease in which the ductal epithelial cells of the breast lose their normal characteristics and proliferate abnormally under the influence of various internal and external carcinogenic factors, so that the cells exceed the limit of self-repair and become cancerous. The main clinical manifestation is breast lumps. Breast cancer is one of the most common malignant tumors in women, with high incidence, aggressive but relatively slow progression, sensitive to radiotherapy, chemotherapy and endocrine therapy, and long natural survival period.
Breast cancer mainly occurs in women, but is rare in men, and the incidence rate of women is nearly 100 times that of men.
2. Overview of the incidence of breast cancer
The incidence of female breast cancer varies significantly between the world, with the United States and Northern Europe being the most prevalent regions, followed by Eastern and Southern Europe and South America, and Asia having the lowest incidence. However, since the 1970s, there has been an increasing trend of incidence in Asia, which was previously a low incidence region, especially in Japan, Singapore and coastal cities of China. This is related to the increase in economic level and lifestyle changes in these regions, so the global gap in the incidence of breast cancer is gradually decreasing.
Generally speaking, it is very rare for women younger than 20 years old to develop breast cancer, and it is not common for women younger than 30 years old to develop the disease. However, from the age of 35, the incidence of breast cancer begins to rise gradually, and in the United States, the incidence increases almost throughout a woman’s life.
3.Risk factors of breast cancer are
(1) Family and heredity
In 1974, Anderson et al. noted that American women who had a first-degree relative with breast cancer were 2-3 times more likely to develop breast cancer than those without a family history, and the relative risk was up to 9 times higher if the first-degree relative had bilateral breast cancer before menopause.
Sometimes breast cancer can be characterized by familial clustering, where at least three relatives in the paternal or maternal line have breast cancer, a family history of both breast and ovarian cancer, and a family history of bilateral and/or young adult breast cancer. In general, familial clustering of breast cancer can be divided into two mechanisms of formation, one due to multiple genetic alterations that lead to breast cancer, and the other due to a single genetic mutation that leads to hereditary breast cancer. Studies in the United States have concluded that only 5% to 10% of breast cancers are caused by some genetic mutation. The majority of women with a family history of breast cancer do not have the aforementioned genetic qualities, and thus their risk is much lower than those with a clear genetic predisposition.
(2) Reproductive factors of women’s breast
Breast cells undergo physiological proliferation due to the cyclical changes of hormone levels in the body every month and the increase of hormone levels in the body during pregnancy. This form of cellular proliferation and division ends at the time of menopause. The occurrence of breast cancer is closely related to many of the reproductive factors mentioned above.
Most studies suggest that age at menarche is associated with both premenopausal and postmenopausal breast cancer. In the United States, a 1-year delay in age at menarche reduces the risk of breast cancer by 20%. Some authors have reported that women of childbearing age with a younger age of menarche have higher hormone levels and shorter menstrual cycles and therefore are more exposed to the endogenous hormonal environment, which may be the main reason for the vulnerability of this group of women to breast cancer;
② Age of menopause: A study in the United States found that the risk of breast cancer for those who undergo menopause before the age of 45 is 1/2 that of those who undergo menopause after the age of 55. It has been confirmed that late menopause is a risk factor for breast cancer, and according to data from the United States, the chance of breast cancer increases by 3% for each year of delayed menopause. Whether it is early menarche or late menopause, women’s menstrual history is actually lengthened, and there are reports that those who have been menstruating for more than 40 years are 1 times more likely to develop breast cancer than those who have been menstruating for less than 30 years.
③Menstrual cycle: It is also agreed that the length of menstrual cycle is one of the risk factors for breast cancer. Studies have found that women with short menstrual cycles between the ages of 20 and 39 have a greater risk of developing breast cancer. This may be because the luteal phase is relatively long in those with short menstrual cycles, and both estrogen and progesterone are high during the luteal phase. Longer menstrual cycles, whether regular or not, reduce the risk of breast cancer.
④ Age at first full-term pregnancy: Numerous epidemiological surveys have found that the risk of breast cancer is greater in infertile women than in women who have had children, and that the younger a woman’s first normal gestation, the lower her lifetime risk of developing breast cancer, but these differences in risk are mainly seen in women diagnosed with breast cancer after age 40, rather than in younger breast cancer patients.
Since the first full-term pregnancy leads to a series of changes in the breast epithelium and the mature epithelium is more resistant to mutations, the earlier the age of the first full-term pregnancy, the less likely the breast tissue is to be affected by internal and external environmental factors that can lead to mutations. However, the decrease in breast cancer risk after pregnancy compared to infertile women is not immediate but takes 10 to 15 years to become clear. In fact, the risk of breast cancer increases within 10 years after the first normal childbirth because the proliferation of breast cells during pregnancy may promote the proliferation of cells that have already undergone mutations, leading to an increased risk of breast cancer within the next 10 years.
The results of a study in Shanghai suggest that the incidence of breast cancer decreases with the increase in the number of births. In addition, recent studies have shown that the shorter the interval between full-term pregnancies, the lower the lifetime risk of breast cancer.
(vi) Breastfeeding history: As early as 1926, there was a hypothesis that women who did not breastfeed were prone to breast cancer. This hypothesis is consistent with the physiology of the breast and breast carcinogenesis, and can explain the phenomenon of regional differences in the incidence of breast cancer, because it is known that breastfeeding is less prevalent and shorter in people in areas with a high incidence of breast cancer than in those with a low incidence. Half of the more than 30 relevant studies have shown that prolonged breastfeeding reduces the risk of breast cancer.
(3) Sex hormone studies
Breast cancer in postmenopausal women is found to be 15% to 24% higher on average than total estrogen levels in healthy women. A large study has now confirmed the correlation between endogenous estrogen and the risk of breast cancer in premenopausal women. Women undergo estrogen replacement therapy after menopause for a variety of reasons, but many studies have found that supplementation with exogenous estrogens increases the chance of breast cancer. Androgens: Most studies do confirm a positive correlation between androgen levels and breast cancer risk in postmenopausal women. Prolactin: High levels of prolactin increase the risk of breast cancer.
(4) Nutritional diet
(1) Fat and high-calorie diet: There is evidence that weight gain is associated with breast cancer, especially after menopause. Some surveys in Shanghai show that the relative risk of breast cancer increases in women who become progressively fatter, especially in women around 60 years of age. In addition, a high-calorie diet during adolescence leads to accelerated growth and development, as well as early menstruation, which leads to prolonged menstruation and weight gain after middle age, which ultimately increases the risk of breast cancer.
②Alcohol: Women who drink alcohol more than 3 times a day have a 50% to 70% increased risk of breast cancer, which may be related to the increase of estrogen level in the body of alcohol drinkers.
③Fiber: Fiber has an inhibitory effect on the occurrence of both breast and colorectal cancer, and studies have found that women who eat less vegetables have a mildly increased risk of breast cancer. It was found that women who ate less vegetables had a mildly increased risk of breast cancer. If the daily intake of fiber was increased to 20g, the risk of breast cancer would be reduced by 15%.
④ Micronutrients: Experimental studies have found that vitamin A-like substances have a protective effect on breast cells. However, so far there is no good evidence that foods rich in vitamin A have the effect of reducing the risk of breast cancer. However, soy protein and its important ingredient Soilbin have been reported abroad to have a significant inhibitory effect on breast cancer development.
Since insulin is one of the growth factors of human breast cancer cells, hyperinsulinemia in type II diabetes can directly promote the development of breast cancer. In addition, insulin levels in the body are negatively correlated with sex hormone binding globulin levels, so high insulin levels can lead to both high estrogen and androgen levels. The relative risk of developing breast cancer is increased in those with lobular or ductal atypical hyperplasia, and has been reported to decrease if breast cancer does not occur within 10 years after diagnosis of atypical hyperplasia.
This shows that even in high-risk histological types, the risk decreases with time. The conventional wisdom has been that lobular carcinoma in situ of the breast is an early histomorphologic manifestation of invasive carcinoma. However, recent evidence suggests that lobular carcinoma in situ is a high-risk factor for breast cancer, a precancerous lesion, and that mastectomy in such patients is a preventive rather than curative measure. The incidence of breast cancer in women after diagnosis of lobular carcinoma in situ increases by approximately 1% per year.