Breast Cancer (intro to cancer)

Introduction to Breast Cancer

  • Presented by: Shereen Nabhani-Gebara, PharmD, BCOP, SFHEA, mBOPA

  • Designation: Professor of Oncology

  • Course Code: PY6011

Epidemiology of Breast Cancer

  • Prevalence:

    • One of the most common cancers in the UK.

    • New Cases: 59,517 reported in 2021.

    • Survival Rate: 76% of women survive beyond 10 years.

    • Mortality Trends: Mortality from breast cancer is declining due to improved measures including:

    • Better screening methods

    • Early detection tactics

    • Advancements in treatment options.

Anatomy of the Human Breast

  • Structures:

    • Lobules: Glandular structures where milk is produced.

    • Ducts: Small tubes that transport milk from lobules to the nipple.

    • Nipple: The raised area on the breast responsible for releasing milk during breastfeeding.

    • Areola: The pigmented area surrounding the nipple.

    • Fat and Connective Tissue: Support and shape the breast.

Risk Factors for Breast Cancer

  • Primary Risk Factors:

    • Gender: Primarily affects females.

    • Age: Increased risk with age.

    • Personal or Family History: A history of breast cancer in relatives increases risk.

    • Radiation Exposure: Previous radiation treatment increases likelihood.

    • Nulliparity: Not having children or having a late first childbirth (>30 years).

    • Hormonal Factors: Including use of oral contraceptives and hormone replacement therapy.

    • Genetic Predisposition: Notably, BRCA1 and BRCA2 mutations.

  • Additional Risk Factors:

    • Menstrual History: Early age of menarche and late age at menopause.

    • Body Fat: Higher body fat is linked to increased risk.

    • Lifestyle Choices: Regular alcohol consumption and tobacco use.

    • Exercise Level: Regular exercise and breastfeeding (>6 months) may reduce risk.

Case Study: Risk Factors Analysis

  • Patient Profile: Mary, 55 years old, postmenopausal, nulliparous, with a family history of breast cancer (mother diagnosed at age 45; sister at age 50).

  • Identified Risk Factors for Mary:

    • Female gender

    • Advanced age

    • Family history of breast cancer

    • History of heavy alcohol consumption

    • High body mass index (BMI of 32).

Breast Cancer Screening in the UK

  • Self-Examination: Recommended as a first step.

  • Mammogram: Offered every 3 years to women between the ages of 50-71 who are registered with a General Practitioner.

Diagnosis of Breast Cancer

  • Triple Assessment Approach:

    • Clinical breast examination

    • Imaging: Mammogram, ultrasound, or MRI scans.

    • Biopsy Procedures:

    • Thin needle biopsy: extracts small tissue samples.

    • Examination of tissue samples under a microscope.

Staging of Breast Cancer (TNM System)

  • Stages: I-IV categorized as:

    • T: Tumor size.

    • N: Number of lymph nodes involved.

    • M: Presence of metastasis.

    • Stage IV: Commonly involved metastasis to bone and brain.

Breast Cancer Staging Details

  • Early Stage (Stage I): Tumor ≤2 cm, not spread to lymph nodes.

  • Locally Advanced (Stages II & III): Tumor size between 2-5 cm, possible spread to lymph nodes and surrounding tissue.

  • Advanced/Metastatic Stage (Stage IV): Tumors have metastasized to distant organs such as lungs, liver, or bone.

Molecular Subtyping of Breast Cancer

  • Hormone Receptors: Types include oestrogen and progesterone receptors.

  • HER2: Overexpression signals aggressive tumor behavior in roughly 20% of patients.

Genetic Testing and Treatment

  • Oncotype DX 21-gene Test: Analyzes specific genes associated with breast cancer recurrence, guiding treatment planning and providing a forecast for the likelihood of recurrence over ten years.

Treatment Modalities

  • Main Categories:

    • Surgery: Approaches vary from radical mastectomy to lumpectomy.

    • Radiotherapy: Used post-surgery in certain cases to minimize recurrence risk.

    • Systemic Anti-Cancer Therapies (SACT): Includes various therapeutic approaches.

Surgical Treatments

  • Types of Surgery:

    • Radical Mastectomy:

    • Removal of the whole breast, pectoral muscles, and axillary lymph nodes.

    • Associated with high postoperative morbidity (e.g., swelling, shoulder dysfunction).

    • Modified Radical Mastectomy:

    • Involves removal of the breast and lymph nodes, potentially followed by radiotherapy based on prognostic factors.

    • Breast-Conserving Surgery: Lumpectomy to remove the tumor, followed by radiotherapy to reduce recurrence risk, with specific contraindications (e.g., previous radiation, pregnancy, T>5cm).

Radiotherapy Specifications

  • Administered following lumpectomy, especially in high-risk patients.

  • Indicated after mastectomy if:

    • Tumor size >5 cm.

    • Positive lymph nodes.

    • Positive or close margins.

Systemic Anti-Cancer Therapies (SACT) Overview

  • Categories of treatment include:

    • Traditional chemotherapy

    • Endocrine (Hormonal) therapy

    • Targeted therapy

    • Immunotherapy

Traditional Chemotherapy Details

  • Neoadjuvant/Adjuvant Strategies:

    • Combinations of chemotherapy agents such as Anthracyclines and Taxanes.

    • Examples:

    • EC regimen: Epirubicin + Cyclophosphamide (6 cycles)

    • AC regimen: Doxorubicin + Cyclophosphamide (4 cycles)

    • with additions of taxane to EC based on lymph node involvement e.g. Docetaxel).

Taxanes and Their Mechanism

  • Phase Specific Drugs: Such as Docetaxel and Paclitaxel, which bind to microtubules, disrupting mitosis and leading to cell death during the M-phase of the cell cycle.

Anthracyclines Mechanism

  • Phase Non-Specific drugs

  • Mechanism of Action: Intercalate with DNA, inhibit DNA helicase, and suppress/inhibits Topoisomerase II activity.

Alkylating Agents Overview

  • Covalent Binding: These agents form cross-links in DNA, arresting the cell cycle and leading to apoptosis.

    • Example: Cyclophosphamide.

Targeted Therapy: Trastuzumab

  • Target: HER2, a protein overexpressed in 20% of breast cancer cases.

  • Effects: Reduces recurrence risk and improves overall survival. Can be administered concurrently or sequentially with chemotherapy - EC followed by concurrent Docetaxel/Trastuzumab, with monitoring for potential cardiotoxicity.

Immune Response Mechanism

  • HER2 Therapy Action: Herceptin binds to HER2 receptors, marking cancer cells for destruction and inhibiting their proliferation by blocking signalling pathways.

Endocrine Therapy Overview

  • Recommended: For all patients with ER-positive (Estrogen Receptor positive) breast cancer.

    • Types:

    • Tamoxifen (for premenopausal women): A selective estrogen receptor modulator (SERM) with both agonistic and antagonistic effects on various tissues.

    • Aromatase inhibitors (postmenopausal women) inhibiting estrogen production from androgens.

Tamoxifen Administration and Considerations

  • Dosage: 20 mg daily.

  • Considerations:
    - needs activation to endoxifen
    - pharmacogenomic implications and interactions with poor metabolisers and CYP2D6 inhibitors e.g. SSRIs like Paroxetine (to be avoided).

Endocrine Therapy in postmenopause

  • tamoxifen

  • aromatase inhibitors - upfront 2-3 yrs post tamoxifen which inhibit conversion of androgens into estrogen (in cases where tamoxifen is not tolerated; these agents reduce estrogen levels and are crucial for improving outcomes in estrogen receptor-positive breast cancer).

Aromatase Inhibitors and Side Effects

  • Types: Third-generation options include Exemestane (steroidal), Anastrozole, and Letrozole (non-steroidal).

  • Common Side Effects: Increased menopausal symptoms (e.g. hot flashes, mood swings, vaginal dryness), musculoskeletal pain, potential for osteoporosis and fractures.

Impact on the Patient

  • Treatment Decisions: Locally advanced or metastatic disease impacts therapy choices between hormonal therapy, chemotherapy, and targeted therapies.

Triple Negative Breast Cancer

  • Characteristics: Lacking estrogen, progesterone, and HER2 receptors, typically treated with traditional chemotherapy and immunotherapy combinations.

  • Example Regimen: includes Epirubicin, Cyclophosphamide, Paclitaxel, and Carboplatin alongside Pembrolizumab.

Metastatic Disease Treatment Approach

  • Initial Treatment Strategies:

    • Chemotherapy if symptomatic visceral metastasis.

    • Hormonal therapy for bone metastases.

    • Bisphosphonates as adjunctive treatment.

Chemotherapy Options for Metastatic Disease

  • Based on prior treatments, single-agent examples include Anthracyclines (liposomal), Capecitabine (oral), and Lapatinib (oral).

Tyrosine Kinase Inhibitor Treatment

  • Lapatinib: An oral therapy for HER2 positive patients, interfering with tumor cell proliferation and inducing apoptosis.

PARP Inhibitors Role

  • Olaparib: Targets tumors with BRCA1 mutations, inhibiting DNA repair and promoting apoptosis. Administered orally.

Role of the Pharmacist in Breast Cancer Treatment

  • Key Responsibilities:

    • Patient consultations including treatment selection based on ER and HER2 status.

    • Precision medicine applications like Tamoxifen regimen verification and dose adjustments for impaired patients.

    • Monitoring patients for drug interactions, specifically between Lapatinib and CYP3A4 inhibitors.

    • Providing supportive care including anti-emetics during treatment.

Further Resources for Breast Cancer Information

  • Educational Materials:

    • Cancer Research UK resources.

    • NCCN guidelines targeting breast cancer.

    • Dr. Liz O’Riordan's social media outreach for patient experiences.

    • Additional pharmacology resources available on YouTube.

    • Charity support for LGBTIQ+ individuals diagnosed with cancer provided by OUTpatients (UK-based).