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Breast Cancer
February 29, 2024
Introduction
 Most common female cancer
 Accounts for 32% of all female cancer
 211,300 new cases yearly and rising
 40,000 deaths yearly
Gross Anatomy
•Sappy’s plexus – lymphatics under areolar complex
•75% of lymphatics flow to axilla
Microscopic Anatomy
 Stromal tissue
 Connective tissue, capillaries, lymphocytes, etc.
 Adipose tissue
 Ductal tissue
 Squamous epithelium
 Columnar or cuboidal
epithelium
 Lobular tissue
Presentation
 Breast lump
 Abnormal mammogram
 Axillary lympadenopathy
 Metastatic disease
Familial Breast Cancer
 Cause 5-10% of all cancer and 25% in women
<30 y/o
 BRCA2
 Causes 40% of familial breast CA
 50-70% - breast
 15-45% - ovarian
 Increased risk for prostate, colon
 BRCA1
 50-70% - breast
 20-30% - ovarian
 Increased risk for prostate, pancreatic, laryngeal,
Screening Mammography
 Recommendations
 Biannually or annually in 40-49 y/o
 Annually in >50 y/o
 15% relative risk reduction
 Birads
 0 - Incomplete assessment; need additional imaging evaluation
 1 - Negative; routine mammogram in 1 year recommended
 2 - Benign finding; routine mammogram in 1 year recommended
 3 - Probably benign finding; short-term follow-up suggested (3%)
 4 - Suspicious abnormality; biopsy should be considered (30%)
 5 - Highly suggestive of malignancy; appropriate action should be
taken (94%)
Biopsy techniques
 FNA
 Diagnostic and therapeutic in cystic lesions
 Core needle
 U/S guided or sterotatic
 90% effective in establishing diagnosis
 Atypia – need excision
 Sterotatic
 Needle localization
 Excision biopsy
Risk of Future Invasive Breast Carcinoma
Based on Histologic Diagnosis from Breast
Biopsies
 No Increase
 Adenosis
Apocrine metaplasia
Cysts, small or large
Mild hyperplasia (>2 but <5 cells deep)
Duct ectasia
Fibroadenoma
Fibrosis
Mastitis, inflammatory
Periductal mastitis
Squamous metaplasia
 Slightly Increased (relative risk, 1.5–2)
 Moderate or florid hyperplasia, solid or papillary
Duct papilloma with fibrovascular core
Sclerosing adenosis, well-developed
 Moderately Increased (relative risk, 4–5)
 Atypical hyperplasia, ductal or lobular
Benign Breast Masses
 Cysts
 Fibroadenoma
 Hamartoma/Adenoma
 Abscess
 Papillomas
 Sclerosing adenosis
 Radial scar
 Fat necrosis
Papilloma
Maligant Breast Masses
 Ductal carcinoma
 DCIS
 Invasive
 Lobular carcinoma
 LCIS
 Invasive
 Inflammatory carcinoma
 Paget’s disease
 Phyllodes tumor
 Angiosarcoma
Ductal carcinoma
DCIS
Ductal carcinoma in situ (DCIS)
 1. Solid type*
 2. Cribiform type
 3. Papillary type
 4. Comedo type*
Lobular carcinoma
Invasive
Histology
A. Ductal NOS
B. Lobular
C.Mucinous
D.Tubular
E. Medullary
Staging
 Tumor
 Tis: in situ
 T1: <2cm
 T2: 2-5cm
 T3: >5cm
 T4: invasion of skin or chest wall
 Node
 N1: 1-3 axillary nodes or int mam node
 N2: 4-9 axillary nodes or palpalbe int mam node
 N3: >10 nodes or combo of axillary and int mam nodes
 {mic micoroscopic posivitiy, mol molecular posiivity
 Metastasis
Staging
Modified Radical Mastectomy
 Entire breast tissue and Level I & II nodes
 Survival at 10 yrs
 Negative nodes – 82% (5% local recurrence)
 Positive nodes – 48% (5% local recurrence)
Simple mastectomy Modified radical
Breast Treatment Trials
 NSABP (1971 with B-04
update in 2002)
 Compared radical, vs modified
radical +/- radiation
 No survival diff for node neg or
pos between three arms
 75% of recurrences occur in 5
years
 Tumor location not important
Breast Treatment Trials
 Ontario study
 All pts got lumpectomy, randomized to radiation or no radiation
 25% failure rate without radiation, 5% with
 NSABP B-06
 Mastecomy vs lumpectomy vs lumpectomy with radiation
 No difference in survival
 39% recur with lumpectomy, reduced to 14% with radiation, 3-4%
with mastectomy
 0.5-1% per year recurrence rate for life with BCT and radiation
 2-5% complication rate with radiation (rib fx, pericarditis, cosmesis)
Radiation after mastectomy?
 2 Danish studies and one Britsh study
 Recommend in: >3 nodes positive,
aggressive/large tumors or extranodal invasion
 Decreased local or regional recurrence
 +/- survival benefit
Sentinel node biopsy
 Contraindications:
 Clinically positive nodes, pregnant or nursing, prior axillary
surgery, locally advanced disease
 False negative rate 3.1%
 Macrometases (>0.2cm) so recommended pathology cuts are
0.2 cm
 Micrometases (IHC staining) 37% death rate vs 50% of those
with macrometases
 If sentinel node positive 43% will have other nodes positive and
24% will have >4 nodes positive
 NSABP (B-32) in progress
Treatment of DCIS
 600% increase after mammography
 Options
 Mastectomy – 1% breast ca mortality
 Large tumors, multicentric, positive margins after
reexcision,
 Lumpectomy and radiation
 Radiation decreases local recurrence by 50%
 Of those that recur 50/50 DCIS vs Invasive
 0-3% chance of dying of maligant breast ca for all
DCIS
Treatment of DCIS
 Nodal involvement
 3.6% of DCIS pts have positive nodes in
mastectomy specimins
 By definition DCIS has no access to lymphatics
 Size may matter (111 DCIS tumors evaluated)
 <45mm – 0% microinvasion
 45-55mm – 17% microinvasion
 >55mm – 48% microinvasion
Tamoxifen in DCIS
 NSABP (B-24)
 Determine benefit of tamoxifen in lumpectomy plus
radiation pts
 31% decrease in ipsilateral, 47% in contralateral,
31% decrease all together
 Retrospectively looked at ER status
 75% of DCIS is ER+
 59% reduction in ER+ pts
 No significant reduction in ER-
Treatment for invasive breast ca
 Locally advanced is likely already metastatic in
most
 Surgery and radiation alone make no difference on survival
 Chemotherapy & +/- Tamoxifen
 Neoadjuvant chemotherapy
 7 randomized trials
 No survival benefit
 50-80% response
 May allow for BCT in large tumors
 Sentinel node before chemo
Tamoxifen
 Indications
 ER + breast ca
 LCIS
 BRCA1/2
 Increased overall risk
 Benefits
 Decreases risk of ca in other breast by 47-80%
 Draw backs
 Increases endometrial ca risk by 2.5, PE 3.0, DVT 1.7
Source: NSABP P-1 trial
Chemotherapy
 Early Breast Cancer Trialists’ Collaborative
Group
 Decreases recurrence (12%) and death (11%) regardless of
nodal status
 Indications
 All patients except node negative, <10mm tumors
 Regimens
 Multidrug combination chemotherapy
 Tamoxifen or aromatse inhibitor - ER positive tumors
 Herceptin (trastuzumab) – HER2/neu positive tumors
 NSABP B-31 – 33% reduction in risk of death
Other breast cancers
 Inflammatory ca
 Carcinoma invading lymphatic ducts
 Chemotherapy, mastectomy, radiation
 50% survival at 5 years
Other breast cancers
Paget’s disease
 Intraepithelial extesion of ductal ca
 Excision with nipple-areolar complex
 Sentinel node if invasive ca
 Mastectomy
Other breast cancers
 Phyllodes tumor
 <1% of breast tumors
 Age 30-45
 Similar in appearance to fibroadenoma
 4% recurrence after excision
 0.9% axillary spread
 Radiation, chemotherapy, tamoxifen ??
Phyllodes tumor Fibroadenoma
Angiosarcoma
 Risk factors
 Radiation
 Lymphedema
 Treatment
 Excision, radiation
Male breast cancer
 90% are invasive at time of diagnosis
 80% ER+, 75% PR+, 30% HER2/neu
 More invade into pectoralis
 Treatment same as for female ca

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Most common female cancer Accounts for 32% of all female cancer

  • 2. Introduction  Most common female cancer  Accounts for 32% of all female cancer  211,300 new cases yearly and rising  40,000 deaths yearly
  • 3. Gross Anatomy •Sappy’s plexus – lymphatics under areolar complex •75% of lymphatics flow to axilla
  • 4. Microscopic Anatomy  Stromal tissue  Connective tissue, capillaries, lymphocytes, etc.  Adipose tissue  Ductal tissue  Squamous epithelium  Columnar or cuboidal epithelium  Lobular tissue
  • 5. Presentation  Breast lump  Abnormal mammogram  Axillary lympadenopathy  Metastatic disease
  • 6. Familial Breast Cancer  Cause 5-10% of all cancer and 25% in women <30 y/o  BRCA2  Causes 40% of familial breast CA  50-70% - breast  15-45% - ovarian  Increased risk for prostate, colon  BRCA1  50-70% - breast  20-30% - ovarian  Increased risk for prostate, pancreatic, laryngeal,
  • 7. Screening Mammography  Recommendations  Biannually or annually in 40-49 y/o  Annually in >50 y/o  15% relative risk reduction  Birads  0 - Incomplete assessment; need additional imaging evaluation  1 - Negative; routine mammogram in 1 year recommended  2 - Benign finding; routine mammogram in 1 year recommended  3 - Probably benign finding; short-term follow-up suggested (3%)  4 - Suspicious abnormality; biopsy should be considered (30%)  5 - Highly suggestive of malignancy; appropriate action should be taken (94%)
  • 8. Biopsy techniques  FNA  Diagnostic and therapeutic in cystic lesions  Core needle  U/S guided or sterotatic  90% effective in establishing diagnosis  Atypia – need excision  Sterotatic  Needle localization  Excision biopsy
  • 9. Risk of Future Invasive Breast Carcinoma Based on Histologic Diagnosis from Breast Biopsies  No Increase  Adenosis Apocrine metaplasia Cysts, small or large Mild hyperplasia (>2 but <5 cells deep) Duct ectasia Fibroadenoma Fibrosis Mastitis, inflammatory Periductal mastitis Squamous metaplasia  Slightly Increased (relative risk, 1.5–2)  Moderate or florid hyperplasia, solid or papillary Duct papilloma with fibrovascular core Sclerosing adenosis, well-developed  Moderately Increased (relative risk, 4–5)  Atypical hyperplasia, ductal or lobular
  • 10. Benign Breast Masses  Cysts  Fibroadenoma  Hamartoma/Adenoma  Abscess  Papillomas  Sclerosing adenosis  Radial scar  Fat necrosis Papilloma
  • 11. Maligant Breast Masses  Ductal carcinoma  DCIS  Invasive  Lobular carcinoma  LCIS  Invasive  Inflammatory carcinoma  Paget’s disease  Phyllodes tumor  Angiosarcoma
  • 13. DCIS Ductal carcinoma in situ (DCIS)  1. Solid type*  2. Cribiform type  3. Papillary type  4. Comedo type*
  • 15. Invasive Histology A. Ductal NOS B. Lobular C.Mucinous D.Tubular E. Medullary
  • 16. Staging  Tumor  Tis: in situ  T1: <2cm  T2: 2-5cm  T3: >5cm  T4: invasion of skin or chest wall  Node  N1: 1-3 axillary nodes or int mam node  N2: 4-9 axillary nodes or palpalbe int mam node  N3: >10 nodes or combo of axillary and int mam nodes  {mic micoroscopic posivitiy, mol molecular posiivity  Metastasis
  • 18. Modified Radical Mastectomy  Entire breast tissue and Level I & II nodes  Survival at 10 yrs  Negative nodes – 82% (5% local recurrence)  Positive nodes – 48% (5% local recurrence) Simple mastectomy Modified radical
  • 19. Breast Treatment Trials  NSABP (1971 with B-04 update in 2002)  Compared radical, vs modified radical +/- radiation  No survival diff for node neg or pos between three arms  75% of recurrences occur in 5 years  Tumor location not important
  • 20. Breast Treatment Trials  Ontario study  All pts got lumpectomy, randomized to radiation or no radiation  25% failure rate without radiation, 5% with  NSABP B-06  Mastecomy vs lumpectomy vs lumpectomy with radiation  No difference in survival  39% recur with lumpectomy, reduced to 14% with radiation, 3-4% with mastectomy  0.5-1% per year recurrence rate for life with BCT and radiation  2-5% complication rate with radiation (rib fx, pericarditis, cosmesis)
  • 21. Radiation after mastectomy?  2 Danish studies and one Britsh study  Recommend in: >3 nodes positive, aggressive/large tumors or extranodal invasion  Decreased local or regional recurrence  +/- survival benefit
  • 22. Sentinel node biopsy  Contraindications:  Clinically positive nodes, pregnant or nursing, prior axillary surgery, locally advanced disease  False negative rate 3.1%  Macrometases (>0.2cm) so recommended pathology cuts are 0.2 cm  Micrometases (IHC staining) 37% death rate vs 50% of those with macrometases  If sentinel node positive 43% will have other nodes positive and 24% will have >4 nodes positive  NSABP (B-32) in progress
  • 23. Treatment of DCIS  600% increase after mammography  Options  Mastectomy – 1% breast ca mortality  Large tumors, multicentric, positive margins after reexcision,  Lumpectomy and radiation  Radiation decreases local recurrence by 50%  Of those that recur 50/50 DCIS vs Invasive  0-3% chance of dying of maligant breast ca for all DCIS
  • 24. Treatment of DCIS  Nodal involvement  3.6% of DCIS pts have positive nodes in mastectomy specimins  By definition DCIS has no access to lymphatics  Size may matter (111 DCIS tumors evaluated)  <45mm – 0% microinvasion  45-55mm – 17% microinvasion  >55mm – 48% microinvasion
  • 25. Tamoxifen in DCIS  NSABP (B-24)  Determine benefit of tamoxifen in lumpectomy plus radiation pts  31% decrease in ipsilateral, 47% in contralateral, 31% decrease all together  Retrospectively looked at ER status  75% of DCIS is ER+  59% reduction in ER+ pts  No significant reduction in ER-
  • 26. Treatment for invasive breast ca  Locally advanced is likely already metastatic in most  Surgery and radiation alone make no difference on survival  Chemotherapy & +/- Tamoxifen  Neoadjuvant chemotherapy  7 randomized trials  No survival benefit  50-80% response  May allow for BCT in large tumors  Sentinel node before chemo
  • 27. Tamoxifen  Indications  ER + breast ca  LCIS  BRCA1/2  Increased overall risk  Benefits  Decreases risk of ca in other breast by 47-80%  Draw backs  Increases endometrial ca risk by 2.5, PE 3.0, DVT 1.7 Source: NSABP P-1 trial
  • 28. Chemotherapy  Early Breast Cancer Trialists’ Collaborative Group  Decreases recurrence (12%) and death (11%) regardless of nodal status  Indications  All patients except node negative, <10mm tumors  Regimens  Multidrug combination chemotherapy  Tamoxifen or aromatse inhibitor - ER positive tumors  Herceptin (trastuzumab) – HER2/neu positive tumors  NSABP B-31 – 33% reduction in risk of death
  • 29. Other breast cancers  Inflammatory ca  Carcinoma invading lymphatic ducts  Chemotherapy, mastectomy, radiation  50% survival at 5 years
  • 30. Other breast cancers Paget’s disease  Intraepithelial extesion of ductal ca  Excision with nipple-areolar complex  Sentinel node if invasive ca  Mastectomy
  • 31. Other breast cancers  Phyllodes tumor  <1% of breast tumors  Age 30-45  Similar in appearance to fibroadenoma  4% recurrence after excision  0.9% axillary spread  Radiation, chemotherapy, tamoxifen ?? Phyllodes tumor Fibroadenoma
  • 32. Angiosarcoma  Risk factors  Radiation  Lymphedema  Treatment  Excision, radiation
  • 33. Male breast cancer  90% are invasive at time of diagnosis  80% ER+, 75% PR+, 30% HER2/neu  More invade into pectoralis  Treatment same as for female ca