breast cancer Flashcards

1
Q

Describe incidence of Bc

A
  • most common cancer in UK
  • 2018 56,000 women got diagnosed and 375 mean
  • 1 in 8 women diagnosed in lifetime

around 12,000 women die and 800 die each year

incidence has increased over time, and mortality has decreased slightly

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1
Q

What are the risk factors of breast cancer

A

- Age (non modifibale)
** - increase risk of breast cancer as you age
- people are living longer so more chances of developing breast cancer
- reasons: immunoscence, DNA changes
- location
** - if you live in developed countries
- socieocencomic
- diet→ obestiy → cancers
**- late 1st pregnancy
**-
early menarche late menopause

- all factors mean more oestrogen exposure
**- oral contraceptive
** - oestrogen chance
- there’s a 14% increase because of pill
- family history
- previous breast cancer
- taking exogenous hormones

- HRT longer you use after menopause
- oestrogen stimulates breast cells to develop cancerous cell
- should not be on for long time, or high dosage
- BMI
- can be modified
- diet etc
- prior radiotherpay
- non hodgkins → radiotherpay to chest
- So may cause breast cancer????
- have to go through a screening

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2
Q

What is breast cancer screening, how it done, and how often

A

-introudced due to forrest report
-early diagnosis allows for a better outcome
- digital mammograms
- every 3 years
- done between ages 50-70 years

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3
Q

What reproductive factors can increase or decrease risk of bc

A
  • Early onset menarche (I)
  • Late menopause (i)
  • Older age at first pregnancy (i)
  • Nulliparity. Each birth reduces the risk by 7% (15% in women with a twin birth). (d)
  • Longer duration of breastfeeding )d)
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4
Q

How does lifestyle factors i.e obesity + alcohol increase risk of breast cancer

looking more at signalling pathways

A
  • Activation of IGF1 and insulin signalling pathways
  • Activation of PI3K/Akt/mTOR signalling pathways
  • Increased production of oestrogen from adipose tissue
  • Increased production of adipokines (e.g. Leptin)

Alcohol
- alcohol metabolism produces → acetaldehyde → which reduced oestrogen metabolism
- Epigenetic changes (DNA methylation)

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5
Q

How can family history affect risk of bc

A
  • Incidence goes up if you have family members that have breast cancer (24x more likely if you have one family member with breast cancer)
  • certain genes like BRCA 1 and 2 have been implicated in breast cancer development
    84x more likely to have breast cancer if one of these genes is mutated
  • BRCA 1 more likely to develop at younger age → more aggressive cancer -> have a basal like subtype
  • BRCA 2 → more likely to be hormone recpetor positive cancer
  • in general population
    • 0.2-0.3 in general pop have these mutations

but 3% of women with breast cancer have mutations in these genes

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6
Q

Where in the breast does most brest cancer come from

A

most breast cancer comes from ducts
i.e dutcal cancer

want to know type→ because of behaviour

  • lobular cancers→ hard to see on a mammogram
  • metaplastic → most aggressive
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7
Q

What two catagories is breast cancer histology broken into

A

In situ
-DCIS, LCIS

Invasive
-around 17 subtypes
-i.r ductal, lobular, tubular, metaplastic etc

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8
Q

What is DCIS

how does it act etc

A
  • ductal carconimia is classed as in situ
  • happens just in cells
  • it doesn’t breech basement membrane → wont go to other organs
  • show up as calcium deposits
  • three grades DCIS → if high grade have a chance of becoming invasive → so need to think fo removal

DCIS is considered a precursor for breast cancer, and its detection and treatment are important for preventing the development of invasive disease.

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9
Q

What is lobular cariconma in situ

A

marker for increased risk of invasive lobular caricinoma

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10
Q

What are the molecular subtypes of breast cancer

A

Basal‐like (BRCA1/ triple‐negative) – 10‐20%
Luminal A (ER+, HER2‐) – 50‐60%
Luminal B (ER+, HER2+) – 10‐20%
HER2 – 10‐15%

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11
Q

How do we diagnose breast cancer

A

Triple assesement

**- clinical
** - examine lump
- examine axilla → lymph nodes
- look for nipple change, skin chnages etc
**- radiological
** - mammogram
- MRI
**- pathological
** - bioposy
- FNA, core biopsy

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11
Q

What are the histological types of bc

A
  • Invasive ductal NST cancer
  • Invasive lobular cancer.
  • Inflammatory breast cancer 1‐5% of all cancers.
    • these are very aggressive
    • spread into lymphatics and blocked it
  • Pagets disease of the nipple
    • looks like eczema
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12
Q

How do we treat bc

A

Neo‐adjuvant therapy

  • Endocrine (aromatase inhibitors)
  • Chemotherapy (anthracyclines and taxanes)
  • Herceptin/Pertuzumab/Lapatinib

Surgery

Adjuvant therapy

  • Endocrine
  • Chemotherapy
  • Radiotherapy
  • Biological agents ( Immunomodulators)
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13
Q

How would we treat small cancer

A
  • breast conserving operation → wide local excision
    • limitation: if the cancer is large its difficulty, because the breast looks a bit different
  • oncoplastic procedures
    • move breast tissues around, and fill the defect
  • mastectomy
    • if there are multiple cancers in one breast
    • or if they have a BRCA gene
      • decrease the chance of reoccurrence
    • small breast, reasonable cancer → removal
    • can have two types of mastectomy → simple, skin sparing mastectomy
  • axillary lymph nodes
    • these are sampled
    • sentienal lymph node biopsy
    • node clearance
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14
Q

What endocrine therapies would you use to treat bc

A
  • Tamoxifen – a competitive inhibitor of estradiol
  • Aromatase inhibitors – significantly lower serum estradiol concentration
  • Ovarian suppression – GnRH agonists suppress ovarian function (Grosselin)
    • surgical oophorectomy to stop oestrogen → prevent cancer from returning
15
Q

Why would do radiotherapy after wide local excison

A

point is to reduce local reoccurrence

16
Q

When do we use chemo in bc and how do we decide

A
  • neo-adjuvant chemo
    • after operation
  • Oncotype test
    • test for certain genes so you don’t expose everyone to chemo
    • score in the previous lecture before this
  • adjuvant chemo
    • look at size, grade, recpetor and lymph node status
    • cycles
    • side effects

decide using oncotype test

17
Q

What biological therapies can you use to treat bc

A

Extracellular mAbs

  • Herceptin/Trastuzumab (HER2)
    • monoclonal antibody
      -binds to HER 2 receptor to inhibit ligand binding
      -promotes ADDC
      -does not block dimmersaition
  • Pertuzumab (HER2)
  • binds to HER2 receptor to stop downstream signalling
  • by blocking dimmeisation

Intracellular TKIs

  • Lapatinib (EGFR/ HER2)
    • targets tyrosine kinase
18
Q

How can we prevent bc

A
  • Diet
  • Alcohol intake
  • Regular exercise
19
Q

immunotherapy and bc

A
  • PDL1 → test breast cancer cells → mainly for triple therapy cancers which are hard to treat
  • PDL1 → a protein on breast cancer cells