Breast Cancer Overview and Epidemiology
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Questions and Answers

What are the primary genes associated with increased breast cancer risk?

  • MLH1 and MSH2
  • BRCA1 and BRCA2 (correct)
  • TP53 and PTEN
  • HER2 and EGFR

    • Triple-negative breast cancer represents 95% of all breast cancer cases.

    False

    What is one method used in chemoprevention to lower breast cancer risk?

    Selective estrogen receptor modulators (SERMs)

    Which statement is true regarding breast masses in pregnant or lactating women?

    <p>They cannot be attributed to benign changes.</p> Signup and view all the answers

    Aromatase inhibitors are effective in lowering the risk of ER-positive breast cancer.

    <p>True</p> Signup and view all the answers

    Which surgical procedures are performed in women with a high genetic risk for breast cancer?

    <p>Prophylactic bilateral oophorectomy and salpingectomy</p> Signup and view all the answers

    Match the term with its description:

    <p>Tamoxifen = A SERM used in chemoprevention ER-positive cancer = Cancer that responds to estrogen Aromatase inhibitors = Lower the risk in postmenopausal women BRCA mutations = Genetic markers for increased breast cancer risk</p> Signup and view all the answers

    Anthracyclines can cause congestive heart failure due to cumulative doses.

    <p>True</p> Signup and view all the answers

    Name one condition that is a contraindication for breast-conserving treatments.

    <p>Large tumor to breast ratio</p> Signup and view all the answers

    Match the following chemotherapy toxicities with their corresponding description:

    <p>Nausea = Common side effect experienced by almost all patients Neutropenia = Reduction in white blood cells leading to increased infection risk Cognitive dysfunction = Commonly referred to as 'chemo-brain' Peripheral neuropathy = Major dose-limiting toxicity of Taxanes</p> Signup and view all the answers

    Which therapy has markedly improved the clinical outcomes of HER2 positive patients?

    <p>Trastuzumab</p> Signup and view all the answers

    Aromatase Inhibitors are examples of targeted anti-HER2 therapies.

    <p>False</p> Signup and view all the answers

    What is the primary benefit of screening mammography?

    <p>Reduces breast cancer mortality</p> Signup and view all the answers

    What is the term used for tumors that are negative for ER, PR, and HER2?

    <p>Triple negative</p> Signup and view all the answers

    Self-examination of the breasts is highly recommended for women aged 45 or older.

    <p>False</p> Signup and view all the answers

    The regimen for chemotherapy must be individualized based on _____, comorbid conditions, and the perspective of the patient.

    <p>prognosis</p> Signup and view all the answers

    Approximately what percentage of breast biopsies leads to a diagnosis of cancer?

    <p>10-20%</p> Signup and view all the answers

    Match the following chemotherapy agents with their class:

    <p>Cyclophosphamide = Alkylating agent Doxorubicin = Anthracycline Fluorouracil = Anti-metabolite Docetaxel = Taxane</p> Signup and view all the answers

    The majority of benign breast masses are due to __________ changes.

    <p>fibrocystic</p> Signup and view all the answers

    Which of the following features is typical for basal-like breast tumors?

    <p>High-grade tumors</p> Signup and view all the answers

    Match the following terms with their descriptions:

    <p>Ductal carcinoma = 85% of invasive breast cancers Fibrocystic changes = Common benign breast mass Atypical hyperplasia = Fourfold greater risk of cancer Screening mammography = Reduces breast cancer mortality</p> Signup and view all the answers

    What is the estimated risk of developing breast cancer for women with atypical hyperplasia?

    <p>Fourfold greater risk</p> Signup and view all the answers

    HER2 positive therapies are equally effective in pre- and post-menopausal women.

    <p>True</p> Signup and view all the answers

    What is characterized by markers of basal/myoepithelial cells?

    <p>Basal-like</p> Signup and view all the answers

    Patients with a benign biopsy and atypical hyperplasia are at little risk of developing breast cancer.

    <p>False</p> Signup and view all the answers

    What age group is recommended for screening mammography?

    <p>45 and older</p> Signup and view all the answers

    The prognosis for the normal breast-like group is similar to the _____ group.

    <p>luminal B</p> Signup and view all the answers

    Match the following breast cancer types with their description:

    <p>HER2 positive = Improved outcomes with targeted therapies Triple negative = Negative for ER, PR, and HER2 Normal breast-like = Gene expression resembles nonmalignant breast epithelium Basal-like = Characterized by high-grade tumors</p> Signup and view all the answers

    A small fraction of women with ductal or lobular cell proliferation has __________% with atypical hyperplasia.

    <p>3</p> Signup and view all the answers

    What findings are primarily associated with benign breast masses?

    <p>Fluid-filled cysts and modest epithelial cell and fibrous tissue hyperplasia</p> Signup and view all the answers

    What is a common characteristic of CLAUDIN-LOW breast cancer?

    <p>Low expression of cell-cell junction proteins</p> Signup and view all the answers

    Patients who achieve a pathologic complete response (PGR) have a worse survival rate compared to those who do not.

    <p>False</p> Signup and view all the answers

    What type of therapy is essential for all patients regardless of response to neoadjuvant chemotherapy?

    <p>Adjuvant endocrine therapy</p> Signup and view all the answers

    Claudin-low breast cancer patients often exhibit __________ infiltration.

    <p>lymphocytic</p> Signup and view all the answers

    Match the type of treatment with its description:

    <p>Modified radical mastectomy = Removal of breast tissue while preserving chest wall muscles Adjuvant endocrine therapy = Treatment for ER-positive breast cancer Neoadjuvant chemotherapy = Chemotherapy given before definitive surgery Adjuvant anti-HER2 therapy = Treatment for HER2 positive breast cancer</p> Signup and view all the answers

    What is often the outcome for many patients undergoing neoadjuvant chemotherapy?

    <p>They are often downstaged</p> Signup and view all the answers

    Triple negative breast cancer is often characterized by high expression of hormone receptors.

    <p>False</p> Signup and view all the answers

    What is one of the primary surgical treatments for breast cancer?

    <p>Modified radical mastectomy</p> Signup and view all the answers

    All patients with HER2 positive cancer should receive __________ therapy.

    <p>adjuvant anti-HER2</p> Signup and view all the answers

    Which type of cell junction protein is LOW in CLAUDIN-LOW breast cancer?

    <p>E-cadherin</p> Signup and view all the answers

    Study Notes

    Breast Cancer Overview

    • Breast cancer is a malignant proliferation of epithelial cells lining the ducts or lobules of the breast.
    • Epithelial malignancies of the breast are the most common cause of cancer in women, excluding skin cancer.
    • Mortality rate from breast cancer has decreased by more than 1/3 over the past three decades in high and middle-income countries.

    Epidemiology and Risk Factors

    • Globally, breast cancer is the second most common cancer and the fourth most common cause of cancer death.
    • In the Philippines, it is the second most common cancer and the second leading cause of death after lung cancer.
    • Seventy-five percent of all breast cancers occur in women aged >50 years.
    • Breast cancer is a sex hormone-dependent disease through increased activity of the estrogen receptor (ER) and its ligands, estradiol, and estrone.
    • Relative exposure to both endogenous and exogenous estrogens increases the risk of breast cancer.

    Risk Factors

    • Early menarche (< 12 years old) increases the risk of breast cancer.
    • Late first full-time pregnancy (> 35 years old) increases the risk of breast cancer.
    • Women without functioning ovaries or who experience early menopause are much less likely to develop breast cancer than those with a normal menstrual history.
    • Hormone replacement therapy (HRT) with conjugated equine estrogens plus progestins nearly doubles the risk of breast cancer.
    • Central obesity, metabolic syndrome, type 2 diabetes, and depression are associated with both occurrence and recurrence of breast cancer.
    • Atypical hyperplasia and radial scars are associated with an increased risk of breast cancer.
    • Prior radiation exposure in adolescence or early childbearing ages can increase the risk of breast cancer.
    • Radioactive iodine therapy for thyroid disease is NOT associated with an increased risk of breast cancer.
    • A woman with a first-degree relative (mother or sister) with breast cancer has an increased relative risk of approximately 30-50%.
    • Only 1-15% of all breast cancers are due to a strong family history.
    • BRCA1 and BRCA2 are breast cancer susceptibility genes. Women who inherit a mutated allele of these genes have a 60–80% lifetime chance of developing breast cancer and a 33% chance of developing ovarian cancer.
    • Cancers that arise within a BRCA1-mutated patient are almost exclusively "triple negative" for estrogen and progesterone receptors (ER, PgR) and human epidermal receptor 2 (HER2).
    • Approximately 20% of women with triple-negative breast cancers are positive for deleterious germline BRCA1 SNPs.

    Screening for Breast Cancer

    • Screening mammography can reduce breast cancer mortality by one-quarter to one-third in women aged ≥50 years.
    • Self-examination or physical breast examination by a health professional is recommended for women aged 45 and older.
    • Self-examination alone has poor sensitivity and specificity and is not recommended.

    Evaluation of Breast Masses in Men and Women

    • Most newly diagnosed breast cancers are asymptomatic.
    • Features that are worrisome for breast cancer include firmness, irregularity, tethering or fixation to the underlying chest wall, and dermal erythema.
    • Persistent lumps in the breast of pregnant or lactating women cannot be attributed to benign changes based on physical findings; such patients should be promptly referred for diagnostic evaluation.
    • Only approximately 1 in 5–10 breast biopsies leads to a diagnosis of cancer.
    • The majority of benign breast masses are due to “fibrocystic” changes.

    Benign Breast Masses

    • A subset of women with ductal or lobular cell proliferation is approximately 30% of patients.
    • The small fraction (3%) with atypical hyperplasia have a fourfold greater risk of developing breast cancer than those women who have not had a biopsy.
    • Patients with a benign biopsy without atypical hyperplasia are at little risk and may be followed routinely.

    Staging

    • Noninvasive breast cancer is classified as either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS).
    • Invasive breast cancers are classified based on origin (ductal, lobular, or mixed) and special types.
    • Staging is performed clinically or pathologically.
    • Staging determines tumor size (T), presence of absence of regional nodes (N), and distant metastasis (M).

    Treatment

    • The goal of therapy for early-stage breast cancer is a cure.
    • Primary therapy for early-stage breast cancer consists of surgery and radiation therapy.
    • Systemic therapy for early-stage breast cancer consists of adjuvant treatment and chemotherapy.

    Subtypes of Breast Cancer

    • Luminal A: These are generally ER-positive, low or negative in HER2, low-grade, and have low proliferative thrust. Prognosis is generally favorable.
    • Luminal B: These are PR negative, may express HER2 but at low levels, usually higher grade and have higher proliferative activity than luminal A tumors. Prognosis is worse than luminal A cancers.
    • HER2 Amplified: These exhibit co-amplification and over-expression of other genes adjacent to HER2. Prognosis was historically poor but has now improved with targeted therapies.
    • Basal: These are negative for ER, PR, and Her2 ("Triple-negative") and characterized by markers of basal/myoepithelial cells. These are usually high-grade tumors and are associated with germline BRCA1 mutations.

    Adjuvant Regimens

    • Endocrine Therapy: Indicated for all patients with ER-positive breast cancer. This includes selective estrogen receptor modulators (SERMs) like tamoxifen and aromatase inhibitors (Al) like letrozole, anazole, and exemestane.
    • Chemotherapy: Multiple-agent adjuvant chemotherapy is more effective than single-agent chemotherapy. Typically, regimens consist of alkylating agents, anthracyclines, anti-metabolites, taxanes, and platinum salts.

    Breast Cancer Subtypes

    • Luminal A
      • Most common
      • ER positive, PR positive, HER2 negative
      • Good prognosis
    • Luminal B
      • ER positive, PR variable, HER2 variable
      • Intermediate prognosis
    • HER2-enriched
      • ER negative, PR negative, HER2 positive
      • Less common
      • Favorable response to anti-HER2 therapy
    • Triple-negative
      • ER negative, PR negative, HER2 negative
      • Most aggressive subtype
      • Often associated with BRCA1 mutations
      • Poor prognosis
    • Normal Breast-like
      • Gene expression similar to nonmalignant breast epithelium
      • Prognosis similar to luminal B group
    • Claudin-low
      • Often triple-negative
      • Low expression of cell-cell junction proteins
      • Frequently associated with lymphocytic infiltration

    Treatment - Local Treatments

    • Modified radical mastectomy
      • Chest wall muscles preserved
      • Sampling of axillary lymph nodes removed
    • Breast-conserving treatments
      • Surgical excision of the primary tumor
      • Followed by loco-regional radiation
    • Contraindications for breast-conserving treatments
      • Large tumor to breast ratio
      • Inability to achieve clear margins with adequate cosmesis
      • Multifocal cancers
      • Extensive four-quadrant DCIS
      • Inability to receive radiation

    Treatment - Neoadjuvant Chemotherapy

    • “Pre-operative”
    • Administered before surgery and radiation
    • Can “downstage” many patients
    • Patients with pathologic complete response (PGR) have improved survival

    Treatment - Adjuvant Endocrine Therapy

    • All patients with ER-positive breast cancer should receive this
    • Can be given orally or via injection
    • Reduces the risk of recurrence

    Treatment - Adjuvant Anti-HER2 Therapy

    • Given to all patients with HER2-positive breast cancer
    • Includes drugs like Trastuzumab and Pertuzumab
    • Reduces risk of recurrence and mortality

    Treatment - Anti-HER2 Therapy

    • Trastuzumab
      • Humanized anti-HER2 monoclonal antibody
      • Given for 12 months
      • Cardiac dysfunction is a main toxicity
    • Pertuzumab + Trastuzumab
      • Significantly reduces distant metastasis and mortality
      • Effective in patients with poor prognostic features like positive axillary lymph nodes

    Chemotherapy Toxicities

    • Common
      • Nausea, vomiting, alopecia
    • Life-threatening or life-changing
      • Neutropenia, fever
      • Secondary myelodysplasia and leukemia
    • Specific Chemotherapy Toxicities
      • Anthracyclines
        • Cumulative dose-related congestive heart failure
      • Taxanes
        • Major dose-limiting and life-changing toxicity of peripheral neuropathy
      • Cognitive dysfunction
        • "Chemo-brain"

    Metastatic Disease

    • 15-20% of patients treated for localized breast cancer develop metastatic disease
    • Occurs in soft tissue, bones, lungs, and liver
    • Many benign conditions can mimic a recurrent breast cancer
    • Treatment can control the disease but rarely cures it

    Risk Factors

    • Family history of breast cancer
    • Early menarche
    • Late first pregnancy

    Features Suggestive of Breast Cancer During Physical Examination

    • Palpable masses
      • Firmness, irregularity
      • Tethering to the underlying chest wall
      • Dermal erythema or peau d’orange
    • Mammography
      • Clustered, heterogenous, linear, and branching microcalcifications
      • Densities

    Cytologic Features of Ductal Carcinoma In Situ (DCIS)

    • Necrosis
    • Poor nuclear grade
    • Comedo subtype
    • Over-expression of HER2

    Important Points on the Exam

    • 52-year-old woman with a family history of breast cancer
      • Family history is a significant risk factor
    • Understand the different types of breast cancers and their prognoses
    • Be able to recognize the signs and symptoms of breast cancer, including during a physical exam
    • Know the different treatment options for breast cancer
    • Be familiar with the common side effects of chemotherapy and other treatments

    Genetic Risk Factors for Breast Cancer

    • Men with a mutant allele of the gene have an increased incidence of prostate cancer and breast cancer.

    Breast Cancer Screening

    • Most newly diagnosed breast cancers are asymptomatic.
    • Screening Mammography
      • Earlier diagnosis and subsequent local and systematic therapy
      • Reduces breast cancer mortality by one-quarter to one-third in women aged ≥50 years.
    • Self-examination or physical breast examination by a health professional
      • Screening for ages 45
      • Poor sensitivity and specificity
      • Not recommended

    Features of Concerning Breast Masses

    • Firmness, irregularity, tethering or fixation to the underlying chest wall, and dermal erythema or follow-up, further evaluation and biopsy (if appropriate) are indicated

    Breast Masses in Pregnancy and Lactation

    • Breast cancer develops in 1 in every 3000–4000 pregnancies
    • Pregnant women often have more advanced disease than premenopausal women.
    • Persistent lumps in the breast of pregnant or lactating women cannot be attributed to benign changes based on physical findings; such patients should be promptly referred for diagnostic evaluation.

    Benign Breast Masses

    • Only approximately 1 in every 5–10 breast biopsies leads to a diagnosis of cancer.
    • Majority of benign breast masses are due to “fibrocystic” changes.
    • A subset of women with ductal or lobular cell proliferation represent approximately 30% of patients.
    • Particularly the small fraction (3%) with atypical hyperplasia have a fourfold greater risk of developing breast cancer than those women who have not had a biopsy.

    Prognosis of Benign Breast Masses

    • Patients with a benign biopsy without atypical hyperplasia are at little risk and may be followed routinely.

    Chemoprevention

    • Selective estrogen receptor modulators (SERMs)
      • Tamoxifen and Raloxifene are effective methods to lower breast cancer risk.
    • Aromatase inhibition in postmenopausal women
      • Lowers risk of ER-positive breast cancer by approximately one-third to one-half.
      • Has no effect on the more lethal ER-negative breast cancers.

    Prophylactic Bilateral Oophorectomy and Salpingo-Oophorectomy

    • Performed in women with high genetic risk (such as those with inherited BRCA1/2 deleterious SNPs).
    • Reduces the risk of ovarian or breast cancer.

    Invasive Breast Cancers

    • 85% are ductal in origin.

    Breast Cancer Treatment

    • Local (Primary) Treatments
      • Modified radical mastectomy
        • Chest wall muscles are preserved: Only a sampling of axillary lymph nodes are removed
        • Surgical excision of the primary tumor (lumpectomy, quadrantectomy, or partial mastectomy) often followed by loco regional radiation
        • Contraindications:
          • Large tumor to breast ratio
          • Inability to achieve clear margins with adequate cosmesis after extensive surgery
          • Multifocal cancers
          • Extensive four-quadrant DCIS
          • Inability to receive radiation
    • Adjuvant Systemic Therapies
      • Endocrine Therapy
        • Tamoxifen or Raloxifene
        • Aromatase Inhibitors (AIs): Letrozole, Anastrozole, Exemestane
        • Reduces risk of distant recurrence and death due to invasive breast cancer
        • Equally effective in pre- and post-menopausal women, but slightly less effective in very young patients.
      • Chemotherapy
        • Multiple-agent adjuvant chemotherapy is more effective than single-agent chemotherapy.
        • Alkylating agent (Cyclophosphamide), anthracyclines (Doxorubicin, Epirubicin), anti-metabolites (5-Fluorouracil, Capecitabine, Methotrexate), taxanes (Docetaxel, Paclitaxel) and the platinum salts (Cisplatin, Carboplatin)
        • Which regimen is appropriate for a patient must be individualized based on prognosis, comorbid conditions, and the perspective of the patient.
      • Neoadjuvant Chemotherapy
        • “Pre-operative”
        • Administration of adjuvant systemic therapy before definitive surgery and radiation therapy
        • Many patients will be “downstaged”
        • Patients who achieve a pathologic complete response (PGR) have a substantially improved survival compared to those who do not.
        • It is essential that all patients, regardless of response to neoadjuvant chemotherapy, receive adjuvant endocrine therapy if they have an ER-positive breast cancer and adjuvant anti-HER2 therapy if their cancer is HER2 positive.
      • Anti-HER2 Therapy
        • Trastuzumab: humanized anti-HER2 monoclonal antibody
          • Decreases both the risk of recurrence and mortality in early-stage breast cancer.
          • Given for 12 months.
        • Cardiac dysfunction: main toxicity, especially when the agent is delivered simultaneously with doxorubicin.
        • Pertuzumab + Trastuzumab: significantly reduces distant metastasis and mortality (in patients with poor prognostic features such as positive axillary lymph nodes).
      • Toxicities of Chemotherapy
        • Nausea, vomiting and alopecia: nearly 100% of patients
        • Potential life-threatening or life-changing toxicities in 2-3% of all treated patients.
          • Neutropenia, fever
          • Secondary myelodysplasia and leukemia
        • Anthracyclines: cumulative dose-related congestive heart failure
        • Taxanes: major dose-limiting and life-changing toxicity of peripheral neuropathy
        • Cognitive dysfunction: “chemo-brain”

    Molecular Subtypes of Breast Cancer

    • Luminal A
      • ER positive, PR positive, HER2 negative
      • Best prognosis
      • Associated with estrogen-responsive tumors
    • Luminal B
      • ER positive, PR positive, HER2 positive
      • High proliferation rate
    • HER2-Enriched
      • ER negative, PR negative (or low), HER2 positive
      • Fast-growing tumors
      • May be associated with more aggressive disease course.
    • Basal
      • Negative for ER, PR and Her2
      • “Triple negative”
      • Characterized by markers of basal/myoepithelial cells.
      • Usually high-grade tumors.
      • Germline BRCA 1 mutations.
    • Normal Breast-Like
      • Gene Expression: reminiscent of nonmalignant “normal” breast epithelium
      • Prognosis is similar to the luminal B group.
    • Claudin-Low
      • Often “triple negative”
      • Low expression of cell-cell junction proteins including E-cadherin.
      • They are frequently associated with lymphocytic infiltration.

    Metastatic Disease

    • 15-20% of patients treated for localized breast cancer develop metastatic disease in the subsequent decade.

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    Description

    This quiz covers important aspects of breast cancer, including its definition, prevalence, and risk factors. Delve into the statistics surrounding breast cancer globally and specifically in the Philippines, and learn about the influence of hormones on the disease. Test your knowledge on a critical health issue that affects many women worldwide.

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