12: Breast Cancer Flashcards

1
Q

Summarise the epidemiology of breast cancer

A

Mainly: post-menopausal women

  • 1/5 of all female cancer deaths
  • 1/9 of women will get breast cancer
  • increasing incidence but decreasing mortality
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2
Q

What is the trend of the incidence in breast cancer in the UK?

A

The incidence is increasing

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3
Q

What is the trend of the mortality rates in breast cancer?

Why?

A

The mortality is decreasing due to

  • Early Diagnosis
  • Better therapies
    • Chemo/Radiotherapies
    • Hormonal Therapies
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4
Q

What kind of tumors are most breast cancers?

A

Normally Carcinomas! (epithelial tissues of ducts)

but might be:

  • e.g. Sarcoma of fatty tissue (rare but agressive)
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5
Q

Explain the strucutre of the ductural epithelium in the mamillary gland

A

The ductural epithelium surrounds the ducts consisting of 2 layers

  1. Luminal epithelium (inner layer)
  2. Outer Myopithelial cells
    1. contract during milk ejection
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6
Q

Which cells are the main site of development of a Mamma Ca?

A

The luminla (inner layer) epithelial cells

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7
Q

How do you call the pre-cancerous state in “breast cancer”?

What are its characteristics?

A

It is called “carcinoma in situ”

  • pre-invasive
  • often: the characterisitcs of individual cells are normal but they have an abnormal growth pattern

Picture: carcinomal im situ of luminal epitheilal cells

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8
Q

What are the differnet forms of cancer that can develop from a mamillary carcinoma in situ?

What is the most common one?

A

Carcinoma in situ can go on and develop differnt types of cancer– >originate in terminal duct lobular unit

  • Lubular carcinoma (10-15%)
  • Infiltrating Ductal Carcinoma, not otherwise specified
    • 80%!
  • Medullary carcinoma, rare, agressive
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9
Q

How do you asses if a Mamma Ca is oestrogen positive or negative?

How many carcinomas show each characteristic?

A

It is done by histological staining with antibodies against human Estrogen Receptor (ER)

  • 80% of IDCs (infiltrating ductal carcinomas) are ER positive!
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10
Q

Explain the location, activation and effect of the Estrogen Receptor and ER activation

A

It is an steroid (intracellular) receptor

  • Estrogen binds to it and releases hsp90
  • Causing dimerisation of ER
  • Travel into cell and alter DNA transcription
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11
Q

Which molecules get expressed via the activation of an Estrogen Receptor?

A

Normally upregulates pro- proliferative and anti-apoptotic factors

  • upregulation of Progesterone Receptor (PR)
  • Cyclin D1
  • c-myc
  • TGF-a
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12
Q

Explain the usuall treatment approach for Breast Cancer

A

Normally

  1. Surgery
    • remove the tumor
  2. Adjuvant therapy –> kill everything that is left behind)
    • radiotherapy
    • chemotherapy
    • endocrine therapy
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13
Q

What is the normal response to Estrogen stimmulation in normal breast cells and in cancerous cells

A

Though activation of ER leads to increased expression of pro-proliferative and anti-apoptotic signals,

  • Normal cells: don’t proliferate/grow themselves but signal adjacent cells to grow (e.g. via TGF)
  • In tumor cells: drives tumor growth
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14
Q

What is the main rationale behind endocrine therapy in breast cancer?

What are the different approaches used?

A

RAtionale: To reduce Estrogen and therefore growth and proliferation of the tumor

  1. In pre-menopausal women: ovarian supression
  2. Blocking estrogen production by enzymatic inhibition
  3. Inhibiting estrogen responses
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15
Q

When would you chosse to treat breast cancer via ovarian supression?

Which strategies do you have?

A

Aim: to reduce Estrogen production in pre-menopausal women

  1. Ovarin ablation
    • surgical oophorectomy
    • Ovarian Irradiation
  2. Supress production of LH/FSH
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16
Q

Explain the process of ovarian ablation in the treatment of breast cancer

What are the disadvantages

A

Reduce estrogen production in pre-menopausal women

  1. Surgical removal
  2. ovarina irradiation (destruction via radiation)

–> Steps are irreversible and lead to infertility, increased morbidity due to risk of procedures

17
Q

Explain the process of hormonal supression in the treatment of breast cancer

A

LHRH Agonist used to supress the production of LH/FSH

  • overstimmulation of LHRH-receptor leads to its downregulation –> less/no response to LHRH
  • reduced Estrogen production
18
Q

Explain the MOA of antiestrogens in breast cancer

A

ER antagonists

  • negate the stimulatory effects of estrogen by blocking the ER, causing the cell to be held at the G1 phase of the cell cycle.
19
Q

Name an example of an anti-estrogenic drug and its clinical use

A

e.g. Tamoxifen

  • used as adjuvant therapy in Breast cancer
  • metastatic disease in postmenopausal patients –> effective and few side effects

Also use as HRT in poastmenopause

20
Q

Explain the effects of Tamoxifan and its use

A

It is a Selective-Estrogen Receptor Modulator (SERM)

  • anti-estrogenic in breast tissue –> blocks growth of cancer cells
  • pro-estrogenic in bone + CVS
    • prevents osteoporosis + enhances estrogenic CVS protection
21
Q

What are the main side-effects of the use of Tamoxifen?

A
  • It increases the riks of thrombosis/embolisms
  • It stimmulates growh of the endometrium –> endrometrial cancer
  • increased frequency of cataracts
22
Q

What are the effects of tamoxifen in contalateral breast cancer/ prevention

A

Reduces the incidence of contralateral breast cancer of 30% –> might be considered as preventative treatement for high risk patients

23
Q

Where does the peripheral enzymatic conversion of androgens to estrogens mainly occur?

A

Mainly in fatty tissue –> breast is a fatty tissue

But also in

  • liver
  • muscle
24
Q

Explain the role of the Progesterone receptor in cancer treatement

A

In advanced cases

  • Progesterone Receptor positive diseases were a lot more likely to respond to treatment
  • Can be used as a target in Breast cancer treatment
25
Q

Which other receptor/Hormone could you use to treat breast cancer?

A

Progesterone Receptors

  • use progestin in breast cancer –> high dose to cause downregulation of receptors and therefore low responses to treatment
  • used in uterine and breast cancer
  • for breast cancer: 2nd/ 3rd line therapy in metastatic disease
  • (megestrol acetate)
26
Q

What is the main issue with endocrine treatments in breast cancer?

A

Resistance

  • expecially in metastatic disease, all patients become resistant
  • But still express ER and are driven by estrogen –> switch from tamoxifen to aromatase inhibitors

–> Use endocrine treatments as long as possible but after that: additional treatment required

27
Q

What are risk factors for developing breast cancer?

A

Mainly: Exposuter to estrogen

  • early onset of menstruation, late menopause
  • age at first full-term pregnancy
  • Forms of contraceptive pill
  • HRT
  • obesity (aromatase in fatty tissue)
  • lDiet, physical activity, height, medication (Aspirin)