Breast Cancer Flashcards

1
Q

Basic pathology breast cancer

A

Sarcomas = rare cancers that arise from the stroma (connective tissue) components which include myofibroblasts and blood vessels cells and cancers arising from these “supportive” cells are phyllodes tumours and angiosarcoma.

Carcinomas = cancers from the epithelial component of the breast which consists of the cells that line the lobules and terminal ducts; under normal conditions these make milk

  • In situ: no invaded breast tissue and the cancer cells grow inside of pre-eisting normal lobules or ducts. COntined within the basement membrane tissue, seen as pre-malignant condition.
    • Ductal carcinoma in situ (DCIS)
    • Lobular carcinoma in situ (LCIS)
  • Invasive: Cancer cells infiltrated outside of normal breast lobules and grow into breast connective tissue. Have the potential to spread to other sides of the body.
    • Invasive ductal carcinoma (75-80%)
    • Invasive lobular carcinoma (10%)
    • Other subtypes – medullary carcinoma or colloid carcinoma
    • Muvinous medullary, papillary (rare)

Pagets disease

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2
Q

RFs invasive carcinoma of the breast

A

: Female sex, age, mutations to certain genes (TSG- BRCA1 BRCA2) , FH , previous benign disease obesity, alcohol consumption, geographic variation, unopposed oestrogen exposure (early menarche, late menopause, nulliparous women, oral contraceptives).

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3
Q

CLinical features of Invasive carcinoma of the breast

A

Breast lump, asymmetry, swelling, abnormal nipple discharge, nipple retraction, skin changes, mastalgia or lump in axilla.

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4
Q

Pagets disease of the nipple

A

rare condition with roughening, reddening and slight ulceration of the nipple. Most have underlying neoplasm. Involvement of epidermis by malignant ductal carcinoma cells and hypothesised they migrate or cells of nipple become malignant.

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5
Q

For a given patient with breast cancer, identify the prognostic factors

A

Nodal status is most important but size, grade and receptor status influence.

Nottingham prognostic index (NPI) = widely used clinicopathological staging system for primary breast cancer prognosis.

(Size x0.2) + Nodal status + Grade

  • Size = diameter lesion in cm
  • Nodal status = number axillary lymph nodes involves (0nodes=1, 1-4=2, >4=3)
  • Grade = based on Bloom Richardson classification

Receptor status is key feature due to new targeted therapy. All malignancies should be checked for oestrogen receptor (ER), Progesterone receptor (PR) and human epidermal growth factor receptor (HER2) status.

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6
Q

Breast Examination

A
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7
Q

Triple Assessment of breast lumps and rationale

A

Hospital based assessment clinic to allow early and rapid detection of breast cancer. Can eb referred to this one stop clinic by GP that meet 2week wait criteria or suspicious finding on mammography. Quick and simple outpatient approach.

  • History + Examination: by breast surgeon or associated specialist, PC, RFs, FH, medications.
  • Imaging:
    • Mammography = compression views of breat across 2 views (oblique and craniocaudal), allowing for detection mass lesions or microcalcifications
    • US scanning = more useful in <35 and in men due to density of breast tissue. Routine for core biopsies too.
    • MRI not used but can be used in assessment of lobular breast cancers with high sensitivity and low specificity.
  • Histology or cytology: Biopsy required of any suspicious mass or lesion presenting to clinic, most commonly via core biopsy.
    • Core biopsy = It provides full histology (as opposed to FNA) allowing differentiation between invasive and in-situ carcinoma. Can give info about grading an dstaging and higher sensitivity/specificity than FNA for detecting breast cancer. Can be tru cut (LA for large lump) or excision(if other investigations fail to give diagnosis) biopy too.
    • If woman has recurrent cytic disease then can be aspirated with FNA to relieve symptoms
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8
Q

Explain the principles of surgical treatment of cancer of the breast

A

All discussed in MDT: breast surgeons, radiologists, oncologists, pathologists and breast cancer specialist nurses for most suitable and patient focused management plan available.

  • Breast conserving: Localised operable disease and no evidence of metastatic disease. Wide local excision is most common with 1cm margin alongside tumour.
  • Mastectomy: Removes all the tissue of affected breast and lots of overlying skin, indicated in multifocal disease, high tumour: breast tissue ratio, disease recurrence or patient choice.
  • Reconstruciton
  • No difference in 5-10year survival

Risk reducing mastectomy:

Remove healthy breast tissue to reduce risk of developing breast cancer. Only for those with high risk and requires counselling. Factors are strong FH breast/ovarian cancer, having BRCA1/ BRCA2/ PTEN/ TP53 mutations or previous history of breast cancer.

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9
Q

Explain the relevance of the assessment of the axilla in the management of breast cancer

A

Nodal status often determines need for systemic therapy, extend of surgery, reconstruction options and need for radiation therapy after surgery.

  • Axillary surgery: mostly alongside WLE and mastectomies to assess nodal status and remove nodal disease.
    • Sentinel node biopsy = remove 1st lymph nodes into which tumour drains (identified through blue dye) and histological analysis
    • Axillary node clearance = remove all nodes in axilla ensuring to not damage any associated important structures within axilla then histological analysis. Common complications are paraesthesia, seroma formation, lymphedema in upper limb
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10
Q

Explain hormonal treatments for cancer of the breast. Name the commonly used hormones.

A

In malignant non-metastatic disease, therapy for breast cancer is adjuvant to reduce risk relapse. Hormone manipulation is the biggest contributor to improved survival (compared with chemo, radioT…)

  • Tamoxifen = Typically in pre-menopausal patients, blocks oestrogen receptors and has role in prophylaxis against breast cancer. Known to increase risk of thromboembolism during and after surgery or periods immobility and increase risk uterine carcinoma.
  • Aromatase inhibitors = (Like anastrozole, letrozole, exemestane) bind to oestrogen receptors and inhibit further malignant growth and preventing further oestrogen production and block conversion of androgens to oestrogen in peripheral tissues. Advised for post-menopausal patients as adjuvant therapy
  • Immunotherapy – Used in patients whose cancer express specific growth factor receptors. Mostly HER-2 positive for which Herceptin (Trastuzumab) is a monoclonal antibody that targets the activity. Can be adjuvant or monotherapy who have had 2 chemo regiments for metastatic breast cancer.

Other Endocrine treatments:

  • Non steroidal aromatase inhibitors – letrozole, anastrozole
  • Steroidal aromatase inhibtiors – exemestane
  • Selective oestrogen receptor degrader – fulvestrant
  • Selective oestrogen receptor modulator – tamoxifen
  • Common toxicities – nausea, hot flushes, swelling of joints, oedema, arthralgia, risk of bone loss, osteoporosis, depression
  • Regular DEXA scan
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11
Q

Oncoplastic Management: Breast cancer

A
  • new approach for extending technique to allow breast conserving surgery or reconstruct breast after mastectomy.
    • Therapeutic mammoplasty – WLE with breast reduction technique and nipple an areola preserved with blood supply
    • Flap formation = latissimus dorsi flap, transverse rectus abdominal muscle flap, deep inferior epigastric perforator flap
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12
Q

Describe, in general terms, adjuvant radiotherapy and chemotherapy in the treatment of breast cancer

A
  • Adjuvant radiation therapy = eradicate any tumour deposits remaining following surgery for patients treated by either breast conserving surgery or mastectomy. Doing so reduces the risk of locoregional recurrence and improves breast cancer specific and overall survivals. Usually if cancer was large, if it spread to lymph nodes in armpit or there were cancer cells close to edge of removed breast tissue.
  • Adjuvant chemotherapy = May have after to reduce the risk of breast cancer coming back. Usually offered it if it has spread to lymph nodes, large, high grade, HER2 positive, triple negative.

Neo-adj vs adj.

  • No differences in long term OS, but slight increase in loco-regional occurrences in NACT
  • NACT favoured as method to assess biology and guide post-operative treatment
  • In HER2 and TNBC, preferred option if tumour >2 cm
  • Carboplatin increases pCR rates in TNBC
  • No prospective randomised data for platinum in TNBC or BRCA1/2 mutations in adjuvant setting
  • Though some retrospective data and is commonly used for BRCA1/2 mutations
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13
Q

Identify which populations are offered breast screening

A

NHS breast cancer screening program 50-71years to have mammogram every 3 years if registered as female on GP and any abnormalities identified to be referred to breast clinic for triple assessment. 71 or over will not automatically be invited but can still have it every 3 years if request it. Mammography

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14
Q

Explain the benefits and potential drawbacks of breast screening

A

Research trials show women with breast screening reduce their risk of dying form breast cancer up to 20% compared to those who do not.

benefits

  • Probably prevent around 1300 women in UK dying form breast cancer every year
  • Cancers found at early syage so treatment more likely to be successful and 80% found then haven’t spread to lymph node.
  • Of found early and small the surgeon can do breast conserving surgery instead of removing the whole breast (and then usually give radiotherapy)

Negatives

  • Cannot prevent cancer
  • Mammograms can be uncomfortable and involves x-rays
  • Results may cause unnecessary worry (false positive)
  • Mammograms may need to be repeated due to burry pc, missing part of breast tissue etc
  • Cancer may be diagnosed between screenings
  • May find cancer than doesn’t need treatment
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15
Q

Red flags for breast cancer

A

redness or flaky skin in nipple area, pulling of nipple or pain in the area. Discharge other than breast milk, including blood an any change in shape or size of breast

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16
Q

Non-malignant breast disease:

A
  • Fibroadenoma – develop form lobules, glandular tissue and ducts grow over and solidify
  • Duct ectasia – Mild ducts shorten and thicken with age/hormones, cause lump/fluid to be expelled
  • Breast pain – beware of inflammatory breast cancer but not this unless other features usually like red and angry
  • Abscess/mastitis- lactating (specific bacteria from baby’s mouth) vs non-lactating breast. Smokers also get lots recurrent abscesses and infection.
  • Breast cysts – can be cyclical. Very hormonal, just fluid in a pocket. Can use needle to drain as uncomfortable.
  • Gynaecomastia – abnormal development of breast tissue in a man. Anabolic steroids can predispose males. Brain tumours etc. Anything that affects hormones. Usually presents with lump on chest wall
  • Fat necrosis – preceding trauma. Fat dies from trauma and forms a lump. Check again in 6w time as if you hit breast lump this can get worse and cause it and bleed (don’t develop cancer from it, you already have it and gets worse )
17
Q

Breats anatomy

A
18
Q

Malignant breast disease:

A
  • DCIS – ductal carcinoma in situ. (Can be thought of as pre cancer). Low (usually revert to normal tissue after time). Intermediate and high grade (usually goes to invasive). Hence why breast screening can be overdiagnosis as surgery etc and yet don’t always develop cancer.
  • LCIS – lobular carcinoma in situ
  • IDC- invasive ductal carcinoma.
  • ILC – invasive lobular carcinoma Lobular carcinoma more likely in both breasts vs ductal.
  • Paget’s disease of the breast – looks like eczema/psoriasis. Always starts at nipple and go outwards rather than eczema is more likely if outside of the nipple. Need biopsy. If clears with steroids then its not cancer and pagets as cancer doesn’t respond to that
19
Q

Pathology of breast cancer

A
  • Cells with damaged DNA do not appotose s they should and get stuck in G0 phase. This cases unregulated replication.
  • BRCA1/BRCA2 etc
  • ER PR HER2 (if ER+ then block oestrogen, same with progesterone and with HER2 give Herceptin)>
  • ‘In Situ’ disease vs local infiltration
  • Staging is measure of spread - TNM
  • Grade is measure of activity or severity.
20
Q

Breast cancer staging

A
21
Q

One stop breast clinic

A
  • Triple assessment – history+ examination, imaging, biopsy
  • P score = palpation, P1 normal, P2lump 100%benign, P3 not sure, P4 more likely cancer, P5 deffo cancer)
  • U score M score = imaging, same principles as above
  • B/C score = biopsy/cytology, (0=no sample, 1=normal, 2=deffo bengin, 3=intermediate, 4=likely cancer, 5=deffo cancer).
  • Scores should match up otherwise you would question reliability.
  • Patients mostly leave with a plan or reassurance
  • History
22
Q

Hsitory in one stop breast clinic

A
  • HPC
  • FH and personal history breast disease
  • PMHx and DHx,
  • Pregnancies- sensitive areas as not all lead to live birth
  • Breast feeding
  • HRT
  • Smoking
  • Alcohol
  • Occupation: typical chemicals like plastic industries, for breast cancer (flight attendants generally at risk of cancer and mostly females so most likely breast cancer due to radiation slightly higher).
  • Exercise tolerance (as may take them for operation)

Bare in mind CT Scan on lactating patient means they absorb more so more at risk of cancer

23
Q

Examination in one stop breast clinic

A
  • Chaeperone
  • Adequate exposure
  • Look, feel, move
  • Look for… dimpling, pea d’ orange, new inversion, discharge (Blood in particular)
  • Movements for…lift arms (squeeze pec muscles as anything causing dimpling will be exaggerated), arms on hips squeeze in
  • Feel each breast in logical sequence, with ipsilateral hand behind head
  • Feel axilla with arm relaxed
  • Feel for supraclavicular and cervical nodes.

Let the arms relax properly or else ruins it

Press and lsight circle for glands, not piano keys

24
Q

Imaging one stop breats clinic

A
  • Ultrasound is targeted investigation
  • Mmamogram is screening tool (40+)
  • Biopsies/cytology
  • Axilla assessment

Normal on left, cancer on right

25
Q

Management breast cancer

A
  • Breast and axillary management are independent of each other – if you have breast cancer they’ll examine lymph nodes in armpit, if nothing in armpit you have breast surgery and take sample in axilla. (sentinel lymph node biopsy) But if something in armpit then you know in op you need to have axillary node clearance.
  • If no axillary issue detected, SLNB (sentinel lymph node biopsy, put radioactive isotope and blue dye in breast and track it draining to lymph nodes and then biopsy that first one that’s blue). This double checks no axillary disease.
  • If axillary disease found, ANC (Axillar node clearance
  • WLE (lumpectomy- lump removed), vs mastectomy. Generally <4cm lumpectomy (bear in mind size of patient breasts as no point WLE if tiny breasts in comparison).
  • Radiotherapy
  • Chemotherapy
  • Oestrogen blockade – only for ER+ cancer for usually at least 5years but preferably 10years if can handle side effects. Don’t want to spark off further growth in case one cell left that’s ER positive. EG Tamoxifen (stops ovaries producing oestrogen for pre-menopausal women), and post-menopausal women and men get letrozole stops fat cells going to oestrogen.
26
Q

Reconstruction in breats surgery - cancer

A
  • Skin preserving, immediate reconstruction, delayed reconstruction. Can have free flap reconstruction, using fat form elsewhere with blood vessels. Can be done at tiem mastectomy or at later time.
  • Prosthesis to go in bra
  • Fat transfer etc
27
Q

clinical features of breast cancer

A
  • Firm, irregular painless lump (may be mobile or fixed it skin or muscle)
  • Pain (10%)
  • Axillary LN involvement
  • Nipple retraction/bloody discharge
  • Paget’s disease
  • Peau d’orange
  • signs of metastatic disease (wt loss)
  • Asymptomatic following screening
28
Q

contorl of systemic disease of breast cancer

A

Control of systemic disease:

  • Radiotherapy (Palliative treatment for bone mets)
  • Chemotherapy (10% survival benefit in younger patients)
  • Hormonal treatment (Tamoxifen 17% survival benefit in older patients)
  • Oopherectomy/LHRH agonists.
29
Q

ALLRED score breats cancer

A

ALLRED SCORE: looks at percentage of cells testing positive for hormone receptors.

Proportion score (cells are ER+ve)

0 No cells

1 ≤ 1% of cells

2 10% of cells

3 11–33% of cells

4 34–66% of cells

5 67–100% of cells

Intensity score

0 Negative

1 Weak

2 Intermediate

3 Strong

Allred score

0–1 No effect

2–3 Small (20%) chance of benefit

4–6 Moderate (50%) chance of benefit

7–8 Good (75%) chance of benefit

30
Q

BRCA cancer risk:

A
  • BRCA1 – 15-45% lifetime risk ovarian cancer and 85% lifetime risk breast cancer
  • BRCA2 – 10-20% lifetime risk ovarian cancer, 85% lifetime risk breast cancer.
  • Bilateral mastectomy reduces risk of breast cancer 90-95% but no survival benefit
  • BRCA1>2 for ovarian cancer risk. prophylactic b/l salpingo-oophorectomy.
  • Test if Strong FH breast/ovarian/pancreatic/prostate cancer, breast cancer before 50, TNBC before 60 and personal history of ovarian cancer, second breast cancer or male.
  • BRCA = TSG, repairs double stranded DNA breask by homologous recombination repair. BRCAs are super sensitive to platinum
    *