Breast Cancer (Mammary Carcinoma): Prevention

Primary prevention

For primary prevention of breast carcinoma, attention must be paid to reducing individual risk factors. Familial breast and ovarian cancer (ovarian cancer).

Women with a high risk of developing breast carcinoma have:

• Mutations in the BRCA1-, BRCA2- RAD 51 C-, and D- genes (the latter are not routinely determined),
• Women at >20% risk of heterozygosity (probability of having a pathogenic mutation in an allele of the known breast cancer genes BRCA1 and BRCA2).
• A residual lifetime risk of > 30%.

(Heterozygote risk and lifetime risk are calculated during genetic counseling using the pedigree according to a standardized prediction model e.g. Cyrill). If BRCA gene status is positive or high risk, the following measures should be offered and discussed during genetic counseling at a designated center:

• Intensified screening
  • Regular clinical self-examination from the age of 18.
  • From the 25.year of age medical clinical examination in combination with mammary sonography (breast ultrasound) every six months.
  • From the age of 25 additionally annual MRI examination until the age of 55 or the involution of the mammary gland parenchyma (regression of breast tissue).
• From the age of 30
  • In addition, annual mammography / X-ray examination of the breast (in case of high breast density from the age of 35) (mammography is of little value due to the high tissue density in young patients. However, it detects up to 18% breast carcinomas that escape MRI [17).
• Surgeries in healthy mutation carriers, BRCA1/2 tested positive.
  • A risk-reducing bilateral prophylactic mastectomy (breast removal bilaterally; RR-BM, also called prophylactic bilateral mastectomy, PBM). In healthy mutation carriers, prophylactic bilateral mastectomy reduces the risk of
    • Of breast carcinoma by >95%.
    • Of breast cancer lethality (breast cancer mortality) by 90%.
• Risk-reducing prophylactic bilateral salpingo-oophorectomy (removal of fallopian tubes and ovaries; RR-BSO) (usually around the age of 40, with completed family planning) is recommended. In this case, there is an indication for hormone replacement therapy until the age of 50. Prophylactic bilateral salpingo-oophorectomy reduces the risk:
  • Of ovarian cancer (ovarian cancer) by 97%.
  • Of breast carcinoma by 50% and
  • That of all-cause mortality by 75%.
  • Surgeries in diseased mutation carriers [18,19]If desired, breast-conserving surgery can be performed because, based on current knowledge, the rate of ipsilateral second cancers does not appear to be significantly increased.There is an increased risk of contralateral “on the opposite side”) breast carcinoma of approximately 25-50% in 15 yearsBilateral (“both sides”) or contralateral mastectomy reduces the incidence of second carcinoma.
  • However, there is no positive effect on overall survival.
  • Prophylactic bilateral salpingo-oophorectomy reduces the risk of contralateral second carcinoma by 30-50%.

For healthy women or women already diagnosed with breast carcinoma from BRCA1/2 negative risk families, the benefit of prophylactic surgery has not been adequately demonstrated. There are currently no studies for primary drug prevention with tamoxifen, GNRHa (gonadotrophin-releasing hormone agonist) + tamoxifen or aromatase inhibitors. Behavioral risk factors

• Diet
  • High-fat diet – A high-fat diet with a high proportion of red meat increases, while a low-fat diet decreases the risk of breast cancer.
  • Red meat, i.e. muscle meat of pork, beef, lamb, veal, mutton, horse, sheep, goat, and meat products increase the risk of breast carcinoma – Red meat is classified by the World Health Organization (WHO) as “probably carcinogenic to humans”, that is, carcinogenic. Meat and sausage products are classified as a so-called “definite group 1 carcinogen” and are thus comparable (qualitatively, but not quantitatively) to the carcinogenic (cancer-causing) effect of tobacco smoking.Meat products include products whose meat component has been preserved or improved in flavor by processing methods such as salting, curing, smoking or fermenting: Sausages, sausage products, ham, corned beef, jerky, air-dried beef, canned meat.
  • High consumption of dairy products or milk (> 230 ml daily) (Adventist Health Study-2 (AHS-2) with about 52,800 participants: +22% and +50% increased risk of breast cancer, respectively).
  • Foods containing acrylamide (Group 2A carcinogen) – formed during frying, grilling, and baking; used to manufacture polymers and dyes; acrylamide is metabolically activated to glycidamide, a genotoxic metabolite; an association between exposure to acrylamide and risk of estrogen receptor-positive breast cancer has been demonstrated.
  • Vitamin D deficiency appears to increase the risk of developing breast carcinoma
  • Eating dinner after 10 p.m. or just before bedtime (risk increase of 16%) versus eating dinner before 9 p.m. or eating the last meal at least 2 hours before bedtime
  • Micronutrient deficiency (vital substances) – see prevention with micronutrients.
• Consumption of stimulants
  • Alcohol (> 10 g/day) – for every 10 g of alcohol per day, the risk of breast cancer increases by 4, 2%.
  • Tobacco (smoking, passive smoking – in women before menopause/time of last spontaneous menstruation in a woman’s life) – That smoking increases the risk of breast cancer has been known for some time. Now a study found that passive smoking may also increase the risk of breast cancer.The researchers also observed a relationship between dose and breast cancer risk: the more and the longer women smoked passively, the greater the increase in the risk of developing breast cancer.
• Late first gravidity (pregnancy) – after the age of 30 – circa three times increased risk.
• Short breastfeeding period – the shorter the breastfeeding period, the higher the risk of developing breast cancer. This revealed a meta-study.
• Psycho-social situation
  • Shift work or night work (+32%), especially the alternation of early, late, and night shifts; may not apply to regular night work – according to the International Agency for Research on Cancer (IARC) assessment, shift work is considered “probably carcinogenic” (group 2A carcinogen)
  • Sleep duration < 6 h and > 9 h is associated with an increased risk of breast carcinoma
• Overweight (BMI ≥ 25; obesity).
  • A five kg/m2 increase in BMI in postmenopause increases risk by a relative 12%; there is a negative association for premenopausal breast carcinoma.
  • Breast cancer patients who are overweight or obese are more likely to suffer from a more aggressive tumor and have lower survival than patients with normal weight.
  • Increased BMI at diagnosis of breast carcinoma is associated with increased all-cause mortality (overall mortality).
• Android body fat distribution, that is, abdominal/visceral, truncal, central body fat (apple type) – there is a high waist circumference or an increased waist-to-hip ratio (THQ; waist-to-hip ratio (WHR)); increased abdominal fat is a risk factor for postmenopausal breast carcinoma and is associated with an increased risk of estrogen receptor-negative breast carcinomaWhen waist circumference is measured according to the International Diabetes Federation guideline (IDF, 2005), the following standard values apply:
  • Women <80 cm

  In 2006, the German Obesity Society published somewhat more moderate figures for waist circumference: < 88 cm for women.

Medication

• Calcium antagonists: long-term therapy > 10 years increases the risk of ductal and lobular breast carcinomas
• Ovulation inhibitors (birth control pills):
  • The use of hormonal contraceptives, in contrast to the protective effect on the emergence to the protective (protective) effect on the emergence of endometrial and ovarian cancer (endometrial and ovarian cancer) increases the risk of developing breast cancer by a factor of 1.2 to 1.5 when taken for more than five years. 5-10 years after stopping ovulation inhibitors, this effect is no longer detectable.
  • The risk of breast cancer increases with duration of use, according to a population-based study, but normalizes within 5 years after cessation of hormonal contraception: the relative risk was 1.20 and was statistically significant with a 95 percent confidence interval of 1.14 to 1.26; the relative risk increased from 1.09 (0.96-1.23) for a duration of use of less than 1 year to 1.38 (1.26-1.51) for a duration of use of more than 10 years.
• Hormone replacement therapy (HRT):
  • There is a slight increase in breast cancer rates under hormone replacement therapy. After a period of use of more than five years, the risk of breast cancer increases by less than 0, 1 % per year (< 1.0 per 1,000 women per year of use). However, this applies only to combination therapy (estrogen-progestin therapy), not to isolated estrogen therapy. For estrogen-only therapy, the median risk was actually lowered after a median duration of use of 5.9 years. Furthermore, when discussing the risk of breast carcinoma, it must be taken into account that hormone application is not responsible for the development of breast carcinoma, i.e., it does not have an oncogenic effect, but merely accelerates the growth of hormone receptor-positive carcinomas. Note: However, the increase in risk is lower than that due to regular alcohol consumption and obesity.
  • Meta-analysis confirms breast cancer risks. Here, type of therapy, treatment duration and body mass index (BMI) are important influencing factors. The following are the most important findings in this regard:
    • Women who started hormone therapy after menopause developed breast cancer more frequently; the risk was also detectable for monopreparations, although the risk was significantly higher for users of combination preparations.
      • Type of therapy
        • Primarily, the incidence of estrogen receptor-positive breast cancer is increased. Breast cancer risk increases with BMI because estrogens are known to be produced in adipose tissue. Regardless, the added risk from estrogens was greater in lean women than in obese women.
        • Use of combined hormone preparations led to 8.3 cases of breast cancer per 100 women in women 50 years of age and older after more than 5 years of use (women who never took hormones and were between 50 and 69 years of age had 6.3 cases of breast cancer per 100 women), i.e., use of combined hormone preparations leads to one additional breast cancer in 50 users.
          • When estrogens combined with intermittent progestin are taken, 7.7 per 100 users develop breast cancer, i.e., taking them leads to an additional breast cancer in 70 users.
        • Taking estrogen monopreparations resulted in 6, 8 cases of breast cancer per 100 women (women who never took hormones and were between 50 and 69 years of age had 6.3 cases of breast cancer per 100 women) after more than 5 years of use, which means one additional cancer for every 200 users.
      • Treatment duration
        • 1-4 years: relative risk of
          • 1.60 for estrogen-progestin combinations.
          • 1.17 for estrogen-monopreparations
        • 5 -14 years: relative risk of
          • 2.08 for estrogen-progestin combinations.
          • 1.33 for estrogen-monopreparations
      • Age of the user at the time of the start of treatment.
        • 45-49 years of age: relative risk of
          • 1.39 for estrogen monopreparations.
          • 2.14 for estrogen-progestin combinations
        • 60-69 years of age: relative risk of.
          • 1.08 for estrogen monopreparations.
          • 1.75 for estrogen-progestin combinations
      • Estrogen receptor-positive tumors (frequency related to duration of use).
      • Intake 5 to 14 years: relative risk of.
        • 1.45 for estrogen monopreparations.
        • 1.42 for estrogen-progestin combinations
      • Estrogen receptor-negative tumors.
        • Intake 5 to 14 years: relative risk of.
          • 1.25 for estrogen monopreparations.
          • 2.44 for estrogen-progestin combinations
        • Varia: For estrogen-only preparations, there was no heterogeneity of risk between equine estrogen and estradiol or between oral administration and transdermal administration.
    • Conclusion: a careful risk-benefit assessment must be made when hormone replacement therapy is used.

X-rays

• Exposure to ionizing radiation

Environmental pollution – intoxications (poisonings).

• Aluminum?
• Dichlorodiphenyltrichloroethane (DDT) – insecticide banned in early 1970s; even prenatal exposure is associated with increased risk of breast cancer: Women in the top third of exposure showed an odds ratio of 5.42, with a wide 95% confidence interval of 1.71 to 17.19, however; women who did not develop breast cancer until after menopause (menopause), aged 50 to 54 years, showed a dose-dependent increase in breast cancer risk; in the top third of exposure, the odds ratio was 2.17 (1.13 to 4.19)
• Hair dye
  • Permanent hair dyes and chemical hair straighteners (risk increase for African American women: 45% if such products were used at least once within the preceding 12 months; 60% if dyeing was done every five to eight weeks; risk increases for white participants, however, were only 7% and 8%, respectively)
  • Cumulative increased risk of estrogen receptor-negative breast cancer, progesterone receptor-negative breast cancer.
• High nighttime exposure to LED light both indoors and outdoors – highest light exposure was associated with a nearly 1.5-fold increased rate of breast cancer
• Polychlorinated biphenyls* (PCBs).
• Polychlorinated dioxin*

* Belongs to the endocrine disruptors (synonym: xenohormones), which even in the smallest amounts can damage health by altering the hormonal system.

Prevention factors (protective factors)

• Genetic factors:
  • Genetic risk reduction depending on gene polymorphisms:
    • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
      • Genes: CASP8, XXCC2
      • SNP: rs1045485 in gene CASP8
        • Allele constellation: CG (0.89-fold).
        • Allele constellation: CC (0.74-fold)
      • SNP: rs3218536 in gene XXCC2
        • Allele constellation: AG (0.79-fold).
        • Allele constellation: AA (0.62-fold)
• Nutrition:
  • Plant-based diet and limited consumption of red meat; applies esp. to postmenopausal women.
  • High-fiber diet during school years and early adulthood.
  • Diet low in fat
  • High vs low consumption of soy is associated with a significantly lower risk of breast cancer (HR) = 0.78; 95% CI:0.63-0.97).
    • Premenopausal women have a 54% lower risk.
    • An evaluation related to hormone receptor status showed a risk reduction for:
      • Estrogen receptor-negative and progesterone receptor-negative breast carcinomas in premenopausal women (HR = 0.46; 95% CI:0.22-0.97).
      • Estrogen receptor-positive and progesterone receptor-positive breast carcinomas in postmenopausal women (HR = 0.72; 95% CI:0.53-0.96).
• Coffee consumption:
  • More than 2 cups of coffee per day was associated with a reduced risk of breast cancer.
  • Increased consumption of caffeinated coffee was associated with a lower risk of postmenopausal breast cancer.
• High versus low leisure-time physical activity is associated with a lower risk of breast cancer (-10%; HR 0.90, 95% CI 0.87-0.93). Other studies even indicate a risk reduction of 20-40%.
• Breastfeeding (> 6 months)
• Weight loss after menopause (time of last menstrual period): postmenopausal women (period that begins when menstruation has stopped for at least a year) who were overweight or obese and not receiving hormone replacement therapy, who reduced their body weight in the first 5 years after menopause and did not regain weight for 5 years thereafter, were significantly less likely to develop breast cancer than women in whom body weight remained the same, based on data an analysis of 10 prospective cohort studies:
  • Weight loss: 4.5-9 kg: breast cancer risk decreased by 25% (hazard ratio 0.75; 0.63 to 0.90)
  • Weight loss: >9 kg: breast cancer risk decreased by 32% (hazard ratio 0.68; 0.50 to 0.93).
• Anorexia nervosa (anorexia): 40% decreased risk of breast cancer. Reasons for the lowered risk are likely caloric restriction and reduced fat weight.
• Medications:
  • U.S. Preventive Service Task Forces (USPSTF) recommendation for drug reduction of breast cancer risk (reduction of estrogen receptor (ER)-positive invasive breast carcinoma) in women at increased risk for breast cancer while at low risk for the side effects of these drugs:
    • Selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene.
    • Aromatase inhibitors
  • Aromatase inhibitor anastrozole postmenopausal [13,18]
    • Anastrozole leads to a reduction in invasive breast cancer in postmenopausal womenDaily use of anastrozole for five years protected postmenopausal women at increased risk from breast cancer beyond the end of treatment in a randomized trial and was able to prevent one in two breast cancers (compared with the pacebo group).
    • Exemestane leads to a reduction in invasive breast cancer in postmenopausal women
  • Nonsteroidal anti-inflammatory drugs (NSAIDs).
    • Taking acetylsalicylic acid (ASA; low-dose ASA: 81 mg/d) at least three times a week: risk reduction of 16%; significant for this was a 20% decrease in risk for HR-positive/HER2-negative tumors.
  • Selective Estrogen Receptor Modulators (SERMs) [14,18]:
    • Tamoxifen leads to reduction of the in women < 35 years of age:
      • Ductal carcinoma in situ
      • Lobular carcinoma in situ
      • Invasive breast carcinoma
    • Raloxifene leads to reduction in invasive breast carcinoma postmenopausally
• Motion:
  • Physical activity reduces the risk of breast cancer by 20-30%. To do this, women should exercise moderately for at least 150 minutes or intensively for 75 minutes per week.

Secondary prevention

Secondary prevention includes early detection of breast cancer in the context of breast self-examination and medical screening, as well as further improvement of therapeutic options. The goal is to detect breast carcinomas or precancerous lesions as early as possible, thereby reducing the number of advanced stages and lowering breast cancer mortality (breast cancer mortality).

• Beginning at age 20, regular monthly breast self-examination is recommended as part of early detection of breast cancer.
• From the age of 30, every woman in Germany is entitled to an annual screening for breast cancer. It includes examination of the breast and lymph node areas (inspection/viewing and palpation/palping), including instructions for self-examination.
• From 50-70 years of age, the screening is supplemented every two years with a mammogram (mammography screening).

Tertiary prevention

Tertiary prevention of breast cancer is about preventing the progression of breast cancer or the occurrence of recurrence. The following measures contribute to this goal:

• Diet
  • Intake of polyunsaturated fatty acids (PUFA; here; fish and long-chain omega-3 fatty acid); reduction in all-cause mortality (total mortality) by 16 to 34%.
  • Women on a low-fat diet had a better prognosis in terms of overall survival than women in the control group who ate a high-fat diet: 10-year overall survival was significantly higher in the intervention group than in the control group (82% vs. 78%).
  • Intermittent fasting (interval fasting): food abstinence (= difference between 24 hours and the phase from the first to the last meal)'[36]: in one study, the probability of recurrence was increased by 36 percent for a food abstinence duration of less than 13 hours during sleep compared with a longer duration (hazard ratio: 1.36; 95% confidence interval between 1.05 and 1.76; p = 0.02). Note: In the study, 80 percent of women with an average age of 52 years were in the early stages (I and II) of breast cancer.
  • Micronutrient deficiency (vital substances) – see therapy with micronutrients.
• Endurance sports (see below breast cancer / sports medicine).
• In a randomized trial in postmenopausal women with receptor-positive breast carcinoma, prolonging hormone therapy with the aromatosis inhibitor letrozole from 5 to 10 years prolonged disease-free survival (but not overall survival). The benefit resulted from prevention of contralateral breast carcinoma, i.e., prevention of new disease rather than prevention of recurrence.