CL1 - Breast & Prostate Cancer

Principles of cancer treatment

aim to kill cancer cells and spare the normal ones

Recent developments to maximise the therapeutic window of cancer treatment

• refine chemotherapy schedules

• nvoel targeted agents

• better supportive medications

• immunotherapy

• tailoring of treatment to individuals

• response predictions

• radiotherapy improvements

Settings for chemotherapy

Adjuvant:

• following surgery or radiotherapy to reduce risk of recurrence

• no way to assess response

• continue to planned number of cycles as long as it is tolerated

Metastatic

• palliative - to control spread of disease

• measure size changes of metastatic lesions

• improvement in symptom control and QoL

Neoadjuvant

• to shrink tumours before surgery or radiotherapy which improves chance of cure

• allows clinical, radiological and pathological response assessments and change to alternative therapy in non-responders

Basic anatomy of the breast

Lymph node areas adjacent to breast

Where the cancer spreads to

• A pectoralis major muscle

• B axillary lymph nodes: level I

• C axillary lymph nodes:  level II

• D axillary lymph nodes:  level III

• E supraclavicular lymph nodes

• F internal mammary lymph nodes (by the heart so cannot be surgically removed)

How do we assess breast lumps?

• history and examination

• mammography

• ultrasound

• MRI

  • DCE-MRI

• Distant staging

  • bone scan

  • CT chest/abdomen/pelvis

  • PET/CT

Staging for Cancer

T: Size of Tumour

N: Rate of Lymph nodes spread

M: Metastases

Tis

Carcinoma in situ - pre-invasive disease

Primary Tumour Staging (T)

• Tis: Carcinoma in situ

• T1: tumour 2cm or smaller in greatest diameter

• T2: Tumour is > 2cm but not > 5cm

• T3: Tumour is > 5cm

• T4: extension to skill or chest wall

Regional Lymph Nodes (N)

N0: no regional lymph node metastasis

N1: Metastasis in 1-3 axillary lymph node(s)

N2: Metastasis in 4-9 axillary lymph node(s) or radiologically involved interanl mammary nodes

N3: Metastasis in 10 or more axillary nodes or ipsilateral infraclavicular lymph nodes

Metastases measure of

Mx: not evaluated

M0: no distant metastases

M1: distant metastases

What do we look out for on pathology reports?

• Tumour type

  • IDC/ILC/papillary/tubular etc

• Associated DCIS/LCIS

• Size

• Grade (1-3)

• Margins

• Lymphovascular invasion

• Nodes

  • Extracapsular spread

• ER/PgR/HER2 receptor status

Pathological type of breast cancer

Invasive ductal carcinoma - most common type

Invasive lobular carcinoma

• more likely multifocal/bilateral

• less likely to present with define lump

• more likely to spread to unusual sites

• but often low grade and more elderly population

• similar long term outcomes

Role of cell surface receptors

• cellular receptors are responsible for translating signals from outside the cell into signals within the cell

• these have effects such as growth, proliferation and cell survival

• can be inappropriately activated in cancer causing the spread and growth of cancer cells

Cell surface receptors in breast cancer

• ER - oestrogen receptor

• PR - progesterone receptor

• Her-2 receptor - overexpressed in ~20% of breast cancers and is associated with more aggressive cancers/poorer prognosis

Why is Her-2 ER negative?

Oestrogen suppresses Her-2 expression and her-2 is overexpressed in cancer

Endocrine therapy

• ER positive tumours are more susceptible to endocrine therapy

• can cause less side effects

• More convenient than chemotherapy

• Lack of cross-resistance

Types of endocrine therapies

• Tamoxifen

• Aromatase inhibitors - anastrozole, letrozole, exemestane

Types of Cancers and their ER responsiveness

Adjunvant chemotherapy in breast cancer

gives absolute survival benefit of around 1-15% depending on patient and tumour characteristics

The combinations have changed over the last 10-15 years

• CMF

• FEC

• TAC/FEC-T

PREDICT BREAST

A programme used to predict the benefit of adjuvant chemotherapy

Inputs data such as:

• pt age

• grade of tumour

• ER responsiveness

Helps make the decision to whether chemotherapy is beneficial when you also consider the SE

Genomic Sequencing

Used to predict the benefit of chemo by sending off a sample of the tumour

• multiple genes examined

• comes up with score for risk of recurrence score

  • less than 11 = low risk

  • 11-25 means intermediate risk

  • > 25 means high risk of recurrence

• used to predict benefit from chemo but made as prognostic marker initially so the high risk could also be in general and not relating to chemo

Initially was only used in node negative but now also being used in node positive patients

Abemaciclib

• cdk 4/6 inhibitor

• given alongside endocrine treatment

• used to double the effect of treatment in metastatic setting

• ~2 year improvement in survival

Issues with Abemaciclib

• toxicity (causes quite a lot of diarrhoea)

• more ANC (absolute neutrophil count)? less nact (neoadjuvant chemo therapy)

• Will pts get a CDK4/6i upon relapse as well?

• 2 years of additional appointments and pharmacy input

Anti-Her2 directed therapy

• Trastuzumab

  • 3-weekly infusions or SC

  • usually given until progression

  • well tolerated but can cause infusion reactions/cardiac effects

• Pertuzumab

  • HER2 dimerisation ibhibitor

  • improves PFS (progression free survival) alongside docetaxel/trastuzumab in 1st line

• Kadcyla

  • TDM1

  • conjugate of trastuzumab and chemotherapy molecule

what is NACT with pembrolizumab?

Neoadjuvant chemo therpay with pembrolizumab

used to treat triple negative breast cancer

seen a higher PCR (pathological complete response)

Use of NACT with pembrolizumab

• longer infusion time in neoadjuvunt setting and additional 9 adjuvant treatments

• clinic time is roughly doubles due to new pt consultation time and due to complex toxicity management

• quite toxic

Metastatic disease

• incurable so the aim is to control and prevent symptoms

• significant gains in PFS and OS (overall survival)

• most patients sequence through 5-6 lines of therapy over a number of years

• similar drugs to adjuvant setting

  • chemo

  • endocrine therapy

  • anti-HER2 therapy

• New agents:

  • Cdk4/6 inhibitors

  • mTOR inhibitors

Trastuzumab Deruztecan

New drug

Her 2 antibody + molecule of chemotherapy attached via linker molecule

targeted chemotherapy so reduced generalised chemo toxicity

Sacituzumab govetican

New drug

Used in triply negative/hormone postive cancers

antibody conjugate: trop-2 antibody + topoisomerase inhibitor

used for advanced breast cancer after 2 or more therapies with at least one of them being intended for advanced disease

Diagnosing Prostate Cancer

• usually through raised PSA blood test

• may or may not have symptoms:

  • bladder frequency

  • nocturia

  • terminal dribbling/poor stream

• digital rectal examination

• MRI scan

• transrectal biopsy

Early detection of prostate cancer

PSA screening and digital-rectal exams can help with early detection and treatment

Prostate cancer pathology

• PSA level

• number of biopsy cores involved

• percentage of tissue involved

• extracapsular extension/seminal vesicle involvement (stage T3a/b)

• lymph node spread (on scans)

• gleason grade:

  • two added scores of 1-5

  • subjective

  • minimum for cancer 3+3=6

Radical Treatment Options

For localised disease

Surgery

• open

• laparoscopic

• robot-assisted

Radiptherapy

• external beam radiotherapy

  • conformal

  • IMRT

  • IGRT

• LDR brachytherapy

• HDR brachytherapy

Active surveillance

Watchful waiting

External beam photon therapy

• targeted treatment

• 20 doses over 4 weeks

• side effects: bowel, bladder and fatigue

Metastatic prostate cancer

Most common spread is to bones

Backbone of treatment is testosterone suppression and blockade e.g.

• LHRHa

• Anti-androgens

• New endocrine therapies: abiraterone, enzalutamide, daralutamide

Chemotherapy

• Docetaxel

• Cabazitaxel

Radium 223

Coping with cancer in the future (NHS)

• Increasing role of independent prescribers

  • decision makers

  • impact on oncology clinics

  • room capacity

• Better horizon planning of impact of new drugs on service

  • ideally centralised

  • lots of work to get accurate estimates

  • impractical to submit business cases for each drug/indication

• Reorganisation of outpatient clinic slots

• Work with RCR/RCP on training and recruitment

• Sensible use of treatments

  • elderly and cdki

  • genomic predictive testing in adjuvant setting

  • later lines of mBC treatments