Breast Cancer

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Basics

Most commonly diagnosed cancer (CA) and the second most common cause of CA death for U.S. women

Description

  • Malignant neoplasm of cells native to the breast—epithelial, glandular, or stroma
  • Types: ductal carcinoma in situ (DCIS), infiltrating ductal carcinoma, infiltrating lobular carcinoma, Paget disease, phyllodes tumor, inflammatory breast cancer (BC), angiosarcoma
  • Molecular subtypes: luminal A (HR+/HER2−), triple negative (HR−/HER2−), luminal B (HR+/HER2+), HER2-enriched (HR−/HER2+)

Epidemiology

Incidence
  • Estimated new female BC cases for in situ: 63,410; invasive: 252,710 in 2017
  • Estimated new male BC cases: 2,470
  • Estimated deaths 2017—females: 40,610; males: 460

Prevalence
>3.5 million U.S. women with a history of BC were alive on January 1, 2016 (1).

Etiology and Pathophysiology

  • Genes such as BRCA1 and BRCA2 function as tumor suppressor genes, and mutation leads to cell cycle progression and limitations in DNA repair.
  • Mutations in estrogen/progesterone induce cyclin D1 and c-Myc expression, leading to cell cycle progression.
  • Additional tumors (33%) may cross-talk with estrogen receptors and epidermal growth factors receptors (EGFR), leading to similar abnormal cellular replication.

Genetics
  • Criteria for additional risk evaluation/gene testing in affected individual
    • BC at age ≤50 years
    • BC at any age and ≥1 family member with BC ≤50 years of age or ovarian/fallopian tube/primary peritoneal CA any age or ≥2 family members with BC or pancreatic CA any age or population at increased risk (e.g., Ashkenazi Jew with BC or ovarian CA at any age)
    • Triple-negative BC (ER−, PR−, HER2−)
    • Two BC primaries in single patient
    • Ovarian/fallopian tube/primary peritoneal CA
    • 1+ family member with BC and CA of thyroid, adrenal cortex, endometrium, pancreas, central nervous system (CNS), diffuse gastric, aggressive prostate (Gleason >7), leukemia, lymphoma, sarcoma, dermatologic manifestations, and/or macrocephaly, gastrointestinal (GI) hamartomas
    • Male BC
    • Known BC susceptibility gene mutation in family
  • Criteria for additional risk evaluation/gene testing in unaffected BC individual
    • First- or second-degree relative with BC ≤45 years of age
    • ≥2 breast primaries in one individual or ≥1 ovarian/fallopian tube/primary peritoneal CA from same side of family or ≥2 w/ breast primaries on same side of family
    • 1+ family member with BC and CA of thyroid, adrenal cortex, endometrium, pancreas, CNS, diffuse gastric, aggressive prostate, leukemia, lymphoma, sarcoma, dermatologic manifestations, and/or macrocephaly, GI hamartomas
    • Ashkenazi Jewish with BC/ovarian CA at any age
    • Male BC
    • Known BC susceptibility gene mutation in family
  • BRCA1 and BRCA2 are inherited in an autosomal fashion and account for 5–10% of female and 5–20% male CAs; 15–20% familial BCs
    • Mutations higher in Ashkenazi Jewish descent (2%)
    • Mutation in BRCA raises risk to 45–65% from 7% at age 70 years.
  • Other BC associated genes: ATM, BARD1, BRIP, CDH1, PTEN, STK11, CHEK2, p53, ERBB2, DIRAS3, NBN, RAD50, RAD51
  • Syndromes associated with BC: Cowden syndrome (PTEN), Li-Fraumeni syndrome (TP53), ataxia-telangiectasia (ATM), and Peutz-Jeghers (STK11)

Risk Factors

  • National Cancer Institute BC Risk calculator: https://bcrisktool.cancer.gov/
  • Hormone Replacement Therapy (combination estrogen-progesterone and estrogen-only agents (but not vaginal estrogen) during perimenopause increases breast cancer risk for 10 years after medication is discontinued.
  • Relative risk (RR) >4.0: age >65 years, biopsy confirmed atypical hyperplasia, BRCA mutation, DCIS, lobular carcinoma in situ (LCIS), personal history of early onset BC (<40 years), two or more first-degree relatives diagnosed at an early age
  • RR 2.1 to 4.0: history of BC (40+ years), postmenopausal, radiation, first-degree relative of BC
  • RR 1.1 to 2.0: EtOH, Ashkenazi Jewish, diethylstilbestrol exposure, early menarche (<12 years), late menopause (>55 years), high socioeconomic status, first pregnancy >30 years, proliferative breast disease without atypia (fibroadenoma or ductal hyperplasia), dense breasts (>50%), never breastfed, no full-term pregnancies, obesity, personal history of endometrial or ovarian CA, hormone replacement therapy, recent oral contraceptive pill use, height (tall)
  • 20–25% lifetime risk should receive an annual MRI beginning at age 30 years: BRCA mutation, first-degree relative with BRCA mutation, history of radiation age 10 to 30 years, Li-Fraumeni or Cowden syndrome or first-degree relative with the same
  • 15–20% lifetime risk: personal history of BC, DCIS, LCIS, atypical ductal hyperplasia, atypical lobular hyperplasia, dense or unevenly dense breasts

General Prevention

  • Maintain healthy weight—obesity increases BC risk; physical activity and healthy diet are key.
  • Limit EtOH—moderate alcohol use increases risk
  • Medication: The U.S. Preventative Services Task Force (USPSTF) recommends that clinicians offer to prescribe risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women who are at increased risk for breast cancer and at low risk for adverse medication effects (B recommendation). The National Cancer Institute Risk Assessment Tool can be used to determine risk. “Greater” risk was defined as >3% where the risk of medication harms are low.
  • Breast self-exams (BSE): American Cancer Society no longer recommend monthly BSE
  • Clinical breast exam (CBE):
    • USPSTF: insufficient evidence to assess clinical benefits and harms
    • American Cancer Society (ACS): no clear benefit or structured guidelines in average-risk women (1)
  • Mammography:
    • USPSTF: women biennial mammogram at age 50 to 74 years
    • ACS: women annual mammograms starting at age 45 years and biennial mammograms at 55 (1)

Commonly Associated Conditions

  • Obesity
  • Genetic syndromes and mutations such as BRCA1, BRCA2, and Li-Fraumeni
  • History of high-risk breast lesions such as atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and LCIS

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Basics

Most commonly diagnosed cancer (CA) and the second most common cause of CA death for U.S. women

Description

  • Malignant neoplasm of cells native to the breast—epithelial, glandular, or stroma
  • Types: ductal carcinoma in situ (DCIS), infiltrating ductal carcinoma, infiltrating lobular carcinoma, Paget disease, phyllodes tumor, inflammatory breast cancer (BC), angiosarcoma
  • Molecular subtypes: luminal A (HR+/HER2−), triple negative (HR−/HER2−), luminal B (HR+/HER2+), HER2-enriched (HR−/HER2+)

Epidemiology

Incidence
  • Estimated new female BC cases for in situ: 63,410; invasive: 252,710 in 2017
  • Estimated new male BC cases: 2,470
  • Estimated deaths 2017—females: 40,610; males: 460

Prevalence
>3.5 million U.S. women with a history of BC were alive on January 1, 2016 (1).

Etiology and Pathophysiology

  • Genes such as BRCA1 and BRCA2 function as tumor suppressor genes, and mutation leads to cell cycle progression and limitations in DNA repair.
  • Mutations in estrogen/progesterone induce cyclin D1 and c-Myc expression, leading to cell cycle progression.
  • Additional tumors (33%) may cross-talk with estrogen receptors and epidermal growth factors receptors (EGFR), leading to similar abnormal cellular replication.

Genetics
  • Criteria for additional risk evaluation/gene testing in affected individual
    • BC at age ≤50 years
    • BC at any age and ≥1 family member with BC ≤50 years of age or ovarian/fallopian tube/primary peritoneal CA any age or ≥2 family members with BC or pancreatic CA any age or population at increased risk (e.g., Ashkenazi Jew with BC or ovarian CA at any age)
    • Triple-negative BC (ER−, PR−, HER2−)
    • Two BC primaries in single patient
    • Ovarian/fallopian tube/primary peritoneal CA
    • 1+ family member with BC and CA of thyroid, adrenal cortex, endometrium, pancreas, central nervous system (CNS), diffuse gastric, aggressive prostate (Gleason >7), leukemia, lymphoma, sarcoma, dermatologic manifestations, and/or macrocephaly, gastrointestinal (GI) hamartomas
    • Male BC
    • Known BC susceptibility gene mutation in family
  • Criteria for additional risk evaluation/gene testing in unaffected BC individual
    • First- or second-degree relative with BC ≤45 years of age
    • ≥2 breast primaries in one individual or ≥1 ovarian/fallopian tube/primary peritoneal CA from same side of family or ≥2 w/ breast primaries on same side of family
    • 1+ family member with BC and CA of thyroid, adrenal cortex, endometrium, pancreas, CNS, diffuse gastric, aggressive prostate, leukemia, lymphoma, sarcoma, dermatologic manifestations, and/or macrocephaly, GI hamartomas
    • Ashkenazi Jewish with BC/ovarian CA at any age
    • Male BC
    • Known BC susceptibility gene mutation in family
  • BRCA1 and BRCA2 are inherited in an autosomal fashion and account for 5–10% of female and 5–20% male CAs; 15–20% familial BCs
    • Mutations higher in Ashkenazi Jewish descent (2%)
    • Mutation in BRCA raises risk to 45–65% from 7% at age 70 years.
  • Other BC associated genes: ATM, BARD1, BRIP, CDH1, PTEN, STK11, CHEK2, p53, ERBB2, DIRAS3, NBN, RAD50, RAD51
  • Syndromes associated with BC: Cowden syndrome (PTEN), Li-Fraumeni syndrome (TP53), ataxia-telangiectasia (ATM), and Peutz-Jeghers (STK11)

Risk Factors

  • National Cancer Institute BC Risk calculator: https://bcrisktool.cancer.gov/
  • Hormone Replacement Therapy (combination estrogen-progesterone and estrogen-only agents (but not vaginal estrogen) during perimenopause increases breast cancer risk for 10 years after medication is discontinued.
  • Relative risk (RR) >4.0: age >65 years, biopsy confirmed atypical hyperplasia, BRCA mutation, DCIS, lobular carcinoma in situ (LCIS), personal history of early onset BC (<40 years), two or more first-degree relatives diagnosed at an early age
  • RR 2.1 to 4.0: history of BC (40+ years), postmenopausal, radiation, first-degree relative of BC
  • RR 1.1 to 2.0: EtOH, Ashkenazi Jewish, diethylstilbestrol exposure, early menarche (<12 years), late menopause (>55 years), high socioeconomic status, first pregnancy >30 years, proliferative breast disease without atypia (fibroadenoma or ductal hyperplasia), dense breasts (>50%), never breastfed, no full-term pregnancies, obesity, personal history of endometrial or ovarian CA, hormone replacement therapy, recent oral contraceptive pill use, height (tall)
  • 20–25% lifetime risk should receive an annual MRI beginning at age 30 years: BRCA mutation, first-degree relative with BRCA mutation, history of radiation age 10 to 30 years, Li-Fraumeni or Cowden syndrome or first-degree relative with the same
  • 15–20% lifetime risk: personal history of BC, DCIS, LCIS, atypical ductal hyperplasia, atypical lobular hyperplasia, dense or unevenly dense breasts

General Prevention

  • Maintain healthy weight—obesity increases BC risk; physical activity and healthy diet are key.
  • Limit EtOH—moderate alcohol use increases risk
  • Medication: The U.S. Preventative Services Task Force (USPSTF) recommends that clinicians offer to prescribe risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women who are at increased risk for breast cancer and at low risk for adverse medication effects (B recommendation). The National Cancer Institute Risk Assessment Tool can be used to determine risk. “Greater” risk was defined as >3% where the risk of medication harms are low.
  • Breast self-exams (BSE): American Cancer Society no longer recommend monthly BSE
  • Clinical breast exam (CBE):
    • USPSTF: insufficient evidence to assess clinical benefits and harms
    • American Cancer Society (ACS): no clear benefit or structured guidelines in average-risk women (1)
  • Mammography:
    • USPSTF: women biennial mammogram at age 50 to 74 years
    • ACS: women annual mammograms starting at age 45 years and biennial mammograms at 55 (1)

Commonly Associated Conditions

  • Obesity
  • Genetic syndromes and mutations such as BRCA1, BRCA2, and Li-Fraumeni
  • History of high-risk breast lesions such as atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and LCIS

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