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Synopsis

  • Discover the broad principles of cancer management using breast cancer as an example, covering
    • Diagnosis
    • Staging
    • Management
    • Prognosis
  • Pull together material covered in the course from a clinican’s perspective

Incidence of different cancers

  • Breast cancer = #2

Incidence of breast cancer in women in Australia

  • Spike around 1995 is due to the advent of BreastScreen

Diagnosis: overview

  • Symptoms patient and screening
  • Risk factors
    • Age
    • Other personal characteristics
    • Family history
    • Past history of cancer
    • Factors in the breast
    • Oestrogen exposure

Risk factors

Family History

  • Younger onset
  • Accounts for 5‐10% of breast cancers <45
  • 1st degree relative < 40 doubles risk
  • Syndromes
    • BRCA1, BRCA2, p53 (p53 is not breast specific)


Oestrogen Exposure

  • Exogenous oestrogen – HRT (HR 1.24)
    • OCP (RR 1.07‐1.24) – DES
  • Endogenous Oestrogen
    • Age of menarche and menopause (longer oestrogen span = higher risk)
    • Parity (more pregnancy = protective)
    • Breast feeding (protective)

Case: Breast lump in a 40yo woman

  • Take a full history and examination
    • (Further investigations do not substitute for a good clinical examination)
  • FH of breast cancer
  • Painless non‐mobile lump
  • Otherwise well
  • Possible diagnosis: other benign and malignant conditions (?)

Other symptoms

  • a new lump or lumpiness, especially if it's only in one breast
  • a change in the size or shape of your breast
  • a change to the nipple, such as crusting, ulcer, redness or inversion
  • a nipple discharge that occurs without squeezing; esp bloodstained
  • a change in the skin of your breast such as redness or dimpling (peau d'orange)
  • an unusual pain that doesn't go away.

How can you help

  • An understanding of what’s going through her mind
  • Appropriate advice
  • Appropriate referrals
  • Appropriate investigations
  • Appropriate knowledge

Diagnosis: malignant or benign

  • Benign
    • Fibroadenoma
    • Cysts
  • Ductal Carcinoma in situ
  • Breast cancer

Diagnosis: Triple assessment

  • Clinical Examination
  • Imaging
  • Pathology: a sample from the lump must be taken
  • Sensitivity 99.6%; Specificity 68%; need all three

Diagnosis: Imaging

  • Breast Imaging
    • Mammogram: a plain x-ray to the breast. Premenopausal women have a lot of glandular tissue, which makes it hard for the x-rays to see the white flecks (microcalcifications) of cancer, so ultrasound is used as well.
    • Ultrasound: doesn't give you a Google Map of the breast, instead you need a systematic scanning technique.
    • MRI: expensive and less expertise since it's a new modality
  • Tissue‐ FNAB, Core biopsy, Excision biopsy
  • Blood tests: to determine the suitability of the subject to undergo certain treatments. Cancer markers aren't that specific for breast cancer.
  • Other imaging: non-breast symptoms (metastatic disease)
  • Surgical referral

What happens next

  • Patient goes to surgery Or
  • Patient has other treatment

Staging

  • Type of cancer (pathology, sample), level of advancement
  • Tumour Node Metastasis (TNM) staging system
  • 4 stage systems
  • Other systems‐ lymphoma, small cell cancer

Staging: T

  • Tx ‐ Primary tumor cannot be assessed.
  • T0 ‐ No evidence of primary tumor.
  • Tis ‐ Carcinoma in situ.
    • Tis(DCIS) ‐ Intraductal Carcinoma in situ.
    • Tis(LCIS) ‐ Lobular Carcinoma in situ.
    • Tis(Paget's) ‐ Paget's disease of the nipple with no tumor.
  • T1 ‐ Tumor 2 cm or less in its greatest dimension.
    • T1mic ‐ Microinvasion 0.1 cm or less in greatest dimension.
    • T1a ‐ Tumor more than 0.1 cm but not more than 0.5 cm in its greatest dimension.
    • T1b ‐ Tumor more than 0.5 cm but not more than 1.0 cm in its greatest dimension.
    • T1c ‐ Tumor more than 1.0 cm but not more than 2.0 cm in its greatest dimension.
  • T2 ‐ Tumor more than 2.0 cm but not more than 5.0 cm in its greatest dimension.
  • T3 ‐ Tumor more than 5 cm in its greatest dimension.
  • T4 ‐ Tumor of any size with direct extension to (a) chest wall or (b) skin as described below:
    • T4a ‐ Extension to chest wall.
    • T4b ‐ Edema (including peau d'orange) or ulceration of the breast skin, or satellite skin nodules confined to the same breast.
    • T4c ‐ Both T4a and T4b.
    • T4d ‐ Inflammatory breast cancer.

See here: wikipedia].

Staging: N (clinical)

  • Nx ‐ regional lymph nodes cannot be assessed. Perhaps due to previous removal.
  • N0 ‐ no regional lymph node metastasis.
  • N1 ‐ metastasis to movable regional axillary lymph nodes on the same side as the affected breast.
  • N2 ‐ metastasis to fixed regional axillary lymph nodes, or metastasis to the internal mammary lymph nodes, on the same side as the affected breast without axillary nodes.
  • N3 ‐ metastasis to supraclavicular lymph nodes or infraclavicular lymph nodes or metastasis to the internal mammary lymph nodes with metastasis to the axillary lymph nodes.

Source is here.


Staging: N (pathological)

  • pN0‐ no nodes
  • pN1‐ 1‐3 nodes
  • pN2‐ 4‐9 nodes
  • pN3‐ 10 or more nodes or
    • Infraclavicular nodes
    • Clinically apparent internal mammary
    • Supraclavicular nodes
  • If it is early stage disease, you expect the nodes to be mobile. Later stage, you expect them to be solid and matted together. Therefore clinical and pathological staging correlate, but pathological staging takes precedence over clinical staging.

Staging: ‘4’stage

  • Stage 0 Tis
  • Stage I T1N0M0
  • Stage IIA T0 or T1, N1 or T2N0
  • Stage IIB T2N1, T3N0 T0‐T2,N2 or T3,N1‐2
  • Stage IIIA T4
  • Stage IIIB N3
  • Stage IIIC M1
  • This matters because it affects treatment.

Staging: Prognosis

  • Tumour factors
    • Type
    • TNM staging
    • Grade
    • Hormone receptor status (sensitivity to oestrogen: this is a prognostic factor, but you also have a class of treatments you can try)
    • Her2 status (her2 = more aggressive cancer)
  • Patient factors
    • Co‐morbidities (e.g. heart disease, other cancer, etc: less fit for treatment)
  • Stage IV

Survival curve

  • Earlier detection = less chance of death
  • Metastatic spread is a poor prognostic indicator

Treatment

Intent

  • Cure: live into the future without cancer
  • Palliation: can't get rid of the tumour completely, set other goals

Modalities

  • Surgery
  • Radiotherapy (unless full mastectomy and axillary node clearance)
  • Chemotherapy (to clean up micrometastatic disease)
    • Cytotoxic chemotherapy
    • Hormonal therapy (anti-estrogen to starve the cancer of this growth factor)
    • Targeted therapies (target specific mutation)
  • Combination and sequential
  • Clinical trials
  • Mastectomy = same outcome as lumpectomy + radiation, except:
  • BRCA1 and BRCA2: best advice is bilateral mastectomy

Surgery

  • Lumpectomy/breast conserving surgery
    • Smaller lesions
    • Sentinel lymph node biopsy
    • Axillary node clearance
      • Level I-III
    • Adjuvant radiotherapy required
    • Better cosmesis
  • Mastectomy
    • Total mastectomy with axillary lymph node clearance
    • Adjuvant radiotherapy not usually necessary - but controversial
    • Factors
      • Multifocal/ill defined DCIS disease
      • Issues with healing-scleoderma/prior XRT
      • Patient choice
      • BRCA

Notes:

  • Axillary clearance --> lymphoedema of arm
  • Adjuvant = additional treatment after surgery to try to eliminate the cancer altogether

Chemotherapy

  • Anthracyclines‐ epirubicin, doxorubicin, pegylated doxorubicin
  • Taxanes‐ paclitaxel, docetaxel
  • Anti‐metabolites‐ capecitabine, fluorouracil, methotrexate, gemcitabine
  • Vinca alkaloid‐ vinorelbine
  • Alkylating agent‐cyclophosphamide
  • Platinum-carboplatin
  • Her2 antagonists‐ trastuzumab, lapatinib
  • Anti‐angiogenesis‐ bevacizumab
  • Anti‐hormonal‐
    • SERM‐tamoxifen,torefimene
    • Aromatase inhibitors‐ anastrozole, letrozole, aromasin
    • GNRH/LHRH agonists‐ goserilin

Chemotherapy

  • Protocols‐ combinations and schedules
    • Eg. AC, AC‐T, TAC, CMF (these are names of different drugs - google it)
  • Dose
    • Body surface area
  • Side effects
    • Common
    • Life threatening (e.g. febrile neutropenia; blood cells killed by chemotherapy)

Radiotherapy

  • External beam and brachytherapy
  • Site
    • Whole breast irradiation
    • Axilla
  • Dose and fractionation
    • Commonly 40‐60 Gray in 25 fractions (5 weeks)
  • Side effects

Combination/sequences

  • Surgery
  • Chemotherapy
    • Neoadjuvant - stage III
    • Adjuvant
    • Palliative
  • Radiotherapy
    • Adjuvant
    • Palliative
  • Hormonal therapy
    • Adjuvant
    • Palliative
  • Multi‐disciplinary team discussion
    • Surgeons, medical and radiation oncologists, nurses, radiologists, pathologists, genetics, palliative care and others
  • Surveillance
    • Local recurrence
    • Distal recurrence
    • New primaries
    • Late side effects

Advanced disease

  • Lung mets with pleural effusion
  • Liver mets
  • Role of the modalities
  • Different priorities:
    • keep well for as long as possible
    • Reduce symptoms
    • Patient’s wishes
  • Pre‐emptive palliation (try out palliative techniques when patient is well to see how they handle it, sort out doses etc)

Palliative care

  • Trying to move away from cigarette butt model to an integrated model
  • Pain control
  • Other symptom control
  • Individual care
  • Community care
  • Psychological issues
  • Spiritual issues
  • Gene profiling: some genetic profiles have poorer prognoses than others

Summary

  • Discover the broad principles of cancer management using breast cancer as an example, covering
    • Diagnosis
    • Staging
    • Management
    • Prognosis
  • Pull together material covered in the course from a clinican’s perspective