Breast Cancer Why Who When What How long Etc. Vernon Harvey - - PowerPoint PPT Presentation

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Breast Cancer Why Who When What How long Etc. Vernon Harvey - - PowerPoint PPT Presentation

Jul 04, 2023 981 likes •1.38k views

Systemic Management of Breast Cancer Why Who When What How long Etc. Vernon Harvey Rotorua, June 2014 Systemic Management of Breast Cancer Metastatic Disease Adjuvant Therapy Aims of therapy Aim of therapy

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SLIDE 1

Systemic Management of Breast Cancer

  • Why
  • Who
  • When
  • What
  • How long
  • Etc…….

Vernon Harvey Rotorua, June 2014

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Systemic Management of Breast Cancer

Metastatic Disease Aims of therapy

  • Quality of life
  • Prolongation of life
  • Identify ‘best’ therapy

Adjuvant Therapy Aim of therapy

  • Enhance cure
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SLIDE 3

Systemic Management of Breast Cancer

Metastatic Disease Options

  • Endocrine therapy
  • Chemotherapy
  • Biological therapy

Adjuvant Therapy Options

  • Endocrine therapy
  • Chemotherapy
  • Biological therapy
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SLIDE 4

Systemic Management of Breast Cancer

Metastatic Disease For whom

  • Symptomatic
  • Fit enough
  • Want therapy

Adjuvant Therapy For whom

  • Dependant on baseline

risk

  • Patient wishes
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SLIDE 5

Metastatic Breast Cancer

Options

  • Endocrine therapy

 ER/PR positive

  • Chemotherapy
  • Biological therapy

 HER2 positive

But which…. Hormones Chemo Chemo Hormones Both together Chemo + Biological

(if HER2 +)

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SLIDE 6
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SLIDE 7

Metastatic Breast Cancer

General Principles Hormone therapy Chemotherapy *

(with Herceptin if HER2+)

Symptom Control * Some prefer chemotherapy first for life threatening disease

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SLIDE 8

Metastatic Breast Cancer

Endocrine Therapy

(ER and/or PR positive)

Tamoxifen Ovarian Ablation

(premenopausal)

Aromatase inhibitors

(postmenopausal)

Progestogens Faslodex Chemotherapy

  • Anthracyclines
  • Taxanes
  • Capecitabine
  • Vinorelbine

Biological Therapy

(HER2 positive)

Trastuzumab (Herceptin) Lapatinib

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Metastatic Breast Cancer

Endocrine Therapy

(ER and/or PR + only)

Single drug Sequential therapy Continue to progression Control in 30-60% Average duration 9- 12 mths Wide variation Chemotherapy

(ER/PR- or failed hormones)

Single or combination Sequential therapy Duration limited by toxicity Control in 30-60% Average duration 9-12 mths Wide variation Achievements

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Adjuvant Therapy of Breast Cancer

Rationale

  • Disease that appears localised may have

spread beyond the breast.

  • Therapy that is only palliative in MBC may

eliminate microscopic disease

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Adjuvant Therapy of Breast Cancer

Options

  • Endocrine therapy

 ER/PR positive

  • Chemotherapy
  • Biological therapy

 HER2 positive

But which….

Hormones (for most ER+) Chemotherapy (depends on risk) Biological (with Chemo)

(if HER2 +)

BUT to whom……..

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Adjuvant Therapy of Breast Cancer The Concept of Risk

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Adjuvant Therapy of Breast Cancer

Assessing the Risk

www.adjuvantonline.com

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Adjuvant Therapy of Breast Cancer

Assessing the Risk

www.adjuvantonline.com

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Adjuvant Therapy of Breast Cancer

Assessing the Risk

www.adjuvantonline.com

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Adjuvant Therapy of Breast Cancer

Assessing the Risk

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Adjuvant Therapy of Breast Cancer

Assessing the Risk

Oncotype DX

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Adjuvant Therapy of Breast Cancer

Effective Therapy - Proportional to Risk

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Adjuvant Therapy of Breast Cancer

Endocrine Therapy

  • ER and/or PR +
  • Most patients (except very low risk)
  • Options

 Tamoxifen  Ovarian Suppression  Premenopausal only  Aromatase Inhibitors  postmenopausal only  preferable for N+ disease

  • Duration

 Tamoxifen 5-10 years  AI

5 years

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ATAC Trial tamoxifenvsanastrazole@ 10 years

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Adjuvant Therapy of Breast Cancer

Endocrine Side-effects

  • Tamoxifen

 Emotional change  Thrombo-embolism (DVT)  Endometrial Cancer

  • Ovarian Suppression

 Menopausal symptoms

  • Aromatase Inhibitors

 Arthralgia  Increased bone loss

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ATLAS Trial 5 vs10 years of tamoxifen

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Adjuvant Therapy of Breast Cancer

Chemotherapy

  • For those at higher risk (? Benefit > 5%)
  • Duration 4 – 8 cycles
  • Side-Effects

 Neutropenic fever  Nausea  Hair Loss  Infertility / Menopausal symptoms  ‘ Chemo’ brain

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Adjuvant Therapy of Breast Cancer

Trastuzumab (Herceptin)

  • HER2 positive only (15% of breast cancer)
  • With chemotherapy
  • Duration 12 months (optimal unknown)
  • Side-effects

 Myocardial dysfunction

 Probably temporary  Long term consequences unknown

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Median follow-up (% follow-up time after selective crossover)

  • No. of DFS events

1 year trastuzumab vs observation

127 vs 220 P<0.0001 218 vs 321 P<0.0001 369 vs 458 P<0.0001

DFS benefit

Favours 1 year trastuzumab Favours observation 1 2 HR (95% CI)

Extended from Gianni et al. Lancet Oncol. 2011.

2005 (0%) 2006 (4.3%) 2008 (33.8%)

1 yr MFU 4 yrs MFU 2 yrs MFU

0.54 0.64 0.76

471 vs 570 P<0.0001 2012 (48.5%)

8 yrs MFU

0.76

Adjuvant Therapy of Breast Cancer

HERA Trial DFS over time

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Adjuvant Therapy of Breast Cancer

Trastuzumab (Herceptin)

  • HERA Trial @ 4 years

D DFS

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  • Better predictors of risk
  • mTOR inhibitors to reverse endocrine

resistance

  • Chemotherapy at about maximum
  • Newer anti-HER2 medications
  • New genetic targets identified

Adjuvant Therapy of Breast Cancer

The Future

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Adjuvant Therapy of Breast Cancer

The Future

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We are moving forward……………

but never as quickly as we want or patients need Thank you

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Back-up slides

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Adjuvant Therapy of Breast Cancer

Assessing the Risk

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MBC – Response to Endocrine therapy

  • Before
  • After 3 months
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Adjuvant Therapy of Breast Cancer

The Effectiveness of Therapy

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Adjuvant Therapy of Breast Cancer

HER2 Family of Genes

neu Erb-b2 HER2 Erb-b3 HER3 Erb-b4 HER4 HRG (NRG1) Tyrosine kinase domain Ligand binding domain Transmembrane

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Systemic Management of Breast Cancer

Metastatic Disease When

  • When symptoms

require

  • Patient need

Adjuvant Therapy When

  • 2-6 weeks post surgery
  • Before surgery for

some large tumours

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SLIDE 37
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Adjuvant Therapy of Breast Cancer

Assessing the Risk