Risk Factors for Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Contemporary breast cancer care:
    • Increasingly relies on a personalized multidisciplinary approach to treatment
  • In order to provide individual counseling of risk:
    • Several risk assessment models are available
  • The most important risk factor for the development of breast cancer is:
    • Gender:
      • The female-to-male ratio for breast cancer is:
        • 100:1
  • Multiple additional factors are associated with an increased risk of developing breast cancer, including:
    • Age, genetic predisposition, a history of proliferative breast disease, prior radiation exposure, a personal or family history of breast cancer, obesity, and hormone exposure
  • Age:
    • According to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program:
      • The incidence of breast cancer increases rapidly:
        • During the fourth decade of life
        • After menopause:
          • The incidence continues to increase but at a much slower rate – peaking in the fifth and sixth decades of life and slowly leveling off during the sixth and seventh decades
      • Approximately one out of eight invasive breast cancers:
        • Will be found in women younger than 45 years
      • Approximately two-thirds of invasive breast cancers:
        • Are found in women older than 55 years
  • Personal and Family History of Breast Cancer:
    • A strong family history of breast cancer:
      • Has been recognized to increase a woman’s risk of breast cancer
    • The overall risk depends on:
      • The number of relatives with breast cancer
      • Their ages at diagnosis
      • Whether the disease was unilateral or bilateral
    • The highest risk is associated with:
      • A young first-degree relative with bilateral breast cancer
    • Overall, the risk of developing breast cancer is increased approximately:
      • 1.5- to 3-fold if a woman has a first-degree relative (mother or sister) with breast cancer
    • A personal history of breast cancer:
      • Is a significant risk factor for the development of cancer in the contralateral breast:
        • With an estimated risk of approximately 0.4% to 1% per year of follow-up (depending on the source)
  • Genetic Predisposition:
    • Hereditary breast cancer secondary to genetic mutations:
      • Accounts for 5% to 10% of all breast cancer
    • Several mutations have been identified to have an increased association with breast cancer risk:
      • Although to varying degrees:
        • These include BRCA1, BRCA2, PALB2, CHEK2, p53 (Li–Fraumeni syndrome), PTEN (Cowden disease), ATM, CDH1, STK11 (Peutz–Jeghers syndrome), and Lynch syndrome
    • Expanded panel genetic testing:
      • Is becoming increasingly common although the penetrance of these mutations and relative risk of breast cancer may vary:
      • Testing of an affected family member:
        • Is recommended to identify and direct testing for a specific genetic loci mutation in unaffected family members
    • Genetic testing:
      • Should be preceded by genetic counseling
    • The most widely studied and known mutations are in the BRCA1 and 2 genes:
      • BRCA1 mutations:
        • Have an estimated lifetime risk of breast cancer of 57% to 65%
        • Have an estimated lifetime risk of ovarian of 10% to 40%
        • They have an increase risk if fallopian tube, peritoneal, pancreatic cancers, and melanoma
      • BRCA2 mutation carriers:
        • Have an estimated breast cancer lifetime risk of 45% to 55%
        • Have an estimated lifetime risk of ovarian of 10% to 20%
        • They and an increase risk of pancreatic, prostate, and higher association with male breast cancers (lifetime risk approximately 5% to 10%) in addition to Fanconi anemia, a syndrome that is associated with childhood solid tumors and development of acute myeloid leukemia
      • BRCA1 and 2 mutation carriers are encouraged to undergo high-risk screening:
        • With annual mammogram alternating with breast MRI or prophylactic mastectomy for risk-reduction
  • Proliferative Breast Disease:
    • Nonproliferative breast diseases:
      • Such as adenosis, fibroadenomas, apocrine changes, duct ectasia, and mild hyperplasia:
        • Are not associated with an increased risk of breast cancer
    • Proliferative breast diseases:
      • Are associated with and increase breast cancer risk to various degrees (RR is 1.5 to 2)
        • Moderate or florid hyperplasia without atypia, papilloma, and sclerosing adenosis carry a slightly increased risk of breast cancer:
          • 1.5 to 2 times that of the general population
        • Atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH):
          • Is associated with a four- to fivefold increased risk of developing breast cancer in either breast
        • Lobular carcinoma in situ (LCIS):
          • Is associated with up to an 8- to 10-fold risk of breast cancer
    • Risk factor modification with chemoprevention in the setting of high-risk lesions:
      • Is highly effective as evidenced by the findings of the NSABP P2 trial:
        • This study found chemoprevention with tamoxifen or raloxifene was associated with a significant decrease in the incidence of invasive and noninvasive breast cancer in the setting of ADH and LCIS:
          • Therefore, consideration of chemoprevention and risk assessment strategies for patients with high-risk lesions should be strongly encouraged
  • Radiation Exposure:
    • Therapeutic radiation exposure to treat disease:
      • Can be a significant cause of radiation-induced carcinogenesis
    • The highest associated risk is seen with higher doses of radiation and radiation treatment given at a young age:
      • Particularly before age 30:
        • Relative risk is 5.2
      • This has been observed in women receiving mantle irradiation for treatment of Hodgkin disease:
        • Given the elevated lifetime risk of breast cancer in this population:
          • High-risk screening with annual mammography and breast MRI is recommended
  • Endogenous Hormone Exposure:
    • The hormonal milieu at different times in a woman’s life may affect her risk of breast cancer:
      • The total duration of exposure to endogenous estrogen:
        • Is an important factor in breast cancer risk
    • Increased risk has been associated with:
      • Early age at menarche
      • Early establishment of regular ovulatory cycles
      • Nulliparity
      • Advanced age at first childbirth
      • Late menopause
    • Interestingly, women who have their first child between ages 30 and 34:
      • Have the same risk as nulliparous women:
        • Whereas women older than 35 years have a greater risk than nulliparous women
    • Obesity can also contribute to endogenous estrogen exposure:
      • Given higher rates of conversion of androgenic precursors through peripheral aromatization in adipose tissue
    • Lifestyle modification:
      • With healthy diet and regular physical activity is beneficial
  • Exogenous Hormone Exposure:
    • Exogenous hormone replacement therapy is a known risk factor for breast cancer:
      • The Women’s Health Initiative, a large-scale prospective study, was abruptly halted in 2002:
        • After interim analysis indicated hormonal replacement therapy (HRT) was associated with:
          • A 26% increase in the risk of breast cancer over a 5-year period
          • As well as an increased risk of stroke and coronary artery disease
      • HRT was found to be associated with increased bone density and fewer menopausal symptoms:
        • Which makes the ongoing use of HRT attractive to many woma
    • A meta-analysis from the Mayo Clinic by Benkhadra et al:
    • Looked at 43 randomized controlled trials and found no association between the use of HRT and cardiac death or stroke
    • Estrogen plus progesterone use:
      • Was associated with a likely increase in breast cancer mortality (relative risk [RR] 1.96 [95% confidence interval (CI) 0.98–3.94])
    • The use of estrogen alone:
      • Did not increase this risk
    • In women who started HRT at less than 60 years of age:
      • There was a reduction in all-cause mortality including cardiovascular and cancer deaths:
        • Overall, the current evidence suggests that HRT does not affect the risk of death from all causes, cardiac death, and death from stroke or cancer
      • Therefore, treating physicians should thoroughly discuss the risks and benefits of this therapy with their patients
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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