Overview of breast ca classification
Overview of DCIS versus LCIS
Ductal carcinoma in situ ( DCIS) definition
Precursor lesion of invasive breast cancer, a neoplastic proliferation of ductal epithelial cells confined to ductal-lobular system without invasion through the basement membrane.
Incidences of DCIS
- Incidence have been increasing since the adoption of MMG screening.
- 25% of all breast cancer in US are DCIS
- 25% of breast cancer diagnosed by MMG are DCIS
- Risk of death/ metastasis for pure DCIS is <1%
- Uncommon in women younger than 30 years, mean age 50 - 59 years.
Presentation of DCIS
- 90% non palpable, asymptomatic & detected by screening
- 10% patient present with palpable mass, nipple discharge, or Paget’s disease
Investigation of DCIS
MMG
- Patients with suspected DCIS should have a diagnostic bilateral mammogram with magnification views to assess the morphology and full extent of any calcifications.
- 70% have microcalcifications without mass
- 30% have microcalcifications with mass on MMG
- 10% patient has mass, density or architectural distortion without calcification
- Usually Multifocal: widespread calcification with extension along mammary ducts towards the nipple.
- Low grade DCIS: Fine, granular calcification.
- High grade DCIS: Coarse granular calcification, linear branching.
Best method of imaging is MRI. MRI has accuracy of 92% vs MMG 56%
-Biopsy either stereotactic biopsy or MRI guided. Vacuum-assisted core biopsy is another option
Diagnosing DCIS
FNAC
- Inadequate to distinguish between invasive and in situ disease (cytology cannot detect stromal invasion).
Core Needle Biopsy (CNB)
- Show tissue architecture to allow diagnosis of DCIS.
- 25% of lesions histologically interpreted as Atypical ductal hyperplasia (ADH) are upgraded to DCIS or invasive cancer after surgical excision.
- 20% DCIS on CNB are IDC after surgical excision.
Types of CNB:
- Stereotactic CNB : imaging performed in at least 2 planes to localize a target lesion in 3 dimensional space
- Ultrasound guided CNB
- Vacuum assisted CNB (Mammotome):
🍎Single insertion
🍎acquisition of contiguous and larger tissue samples
🍎10x the tissue of core needle biopsy ( higher sensitivity and specificity than core biopsy)
HWL (Hook wire Localization & Excision)
- Indicated in patient unsuitable for stereotactic biopsy & lesion not detectable by U/S
- Most DCIS is unicentric
- Only 1% shows multicentric
- Multicentric tumor – separate foci of tumor found in > 1 quadrant or >5cm away from primary tumor.
- Multifocal tumor - separate tumor foci within the same quadrant.
DCIS pathological subtypes
🔥1) Comedo :
Atypical cells with abundant luminal necrosis filled within the duct- cells are large with pleomorphic nuclei & abnormal mitosis- necrotic material calcifies leading to microcalcification in MMG
🔥2) Non - Comedo:
-Micropapillary - small tufts of cells that project into the lumen. Lack fibrovascular cores. Pure micropapillary patterns may indicate extensive disease within the breast.
-Papillary - Intraluminal projections of tumor cells with fibrovascular cores (true papillations)
-Cribriform - Formation of spaces in between groups of cancer cells like Swiss cheese.
-Solid - Space completely filled by tumor cells.
🔥3) Other rarer subtypes:
- Neuroendocrine
- Apocrine
- Signet cell
Nuclear Grading of DCIS
- DCIS also graded into Low, Intermediate and High risk DCIS base on nuclear grading, architectural pattern, necrosis and polarization
- DCIS progression to IBC occurred in 40% of patients (median age 30 years)
Management of DCIS
-10 times higher risk of developing ipsilateral invasive breast if untreated.
-Surgery is the mainstay of management.
-LR can be predicted using Van Nuys Prognostic Score (VNPI) ; taking into consideration 3 factors- tumor size, margin and pathological grade
-Some author suggest treatment base on VNPI; BCS alone in low risk, BCS+RT in moderate risk and mastectomy in high risk
-BCS can be considered as first option but associated with high rate LR, majority of LR are invasive (50%) with 20% metastatic disease
-🚨Indication for mastectomy (MX)
1. Tumor >4cm
2. Multicentric lesion
3. Inadequate margin
4. Recurrence after BCS
-MX has 98% local control in 7 years with recurrence rate of 1.5%
-DCIS patient undergo MX is ideal candidate for immediate recons due to no radiotherapy needed and no nodal involvement
What are the prognostic index used to predict RT in patient with BCS for DCIS
Van Nuys Prognostic Index 2003 can be used to guide decision for RT in patient with BCS to prevent over treatment.
Reasons of local recurrence of DCIS
LR affected by many reasons:
- Size of tumor; a study reported LR 10% vs 50% in 10 years for tumor < 10mm compared to >10mm
-Margin clearance; French guidelines advocate for ≥3mm and re- excision if margin <1mm. Meta- analyses showed margin ≥2mm superior than
lesser margin
-Grade of DCIS
Indication of Sentinel lymph node biopsy in DCIS
- Most patients not indicated for SLNB as axillary nodes are rarely positive for DCIS <1%.
Indication:
-High risk features:
Define low risk as DCIS that is low- or intermediate-grade, small (<2.5 cm in size), and resected with widely negative margins (≥1 cm).
-Microinvasive breast carcinoma
-Patient undergoing mastectomy (lymphatics anatomy altered)
-No role of axillary dissection in DCIS
🔥Indication for SLNB:
- Absolute: histologically confirmed concurrence or recurrence disease
- Relative: Patient going for MX (difficulty of SLNB later), high risk of invasive disease (palpable lump, comedo necrosis)
Role of Endocrine Therapy in DCIS
Indication:
- ER-positive DCIS (50 – 75% DCIS) who have not undergone a bilateral mastectomy.
- ER-negative - not routinely given as chemoprevention but may opt for ET to decrease risk of developing new ER-positive DCIS or invasive cancer.
- Bilateral mastectomies for DCIS ET not indicated (risk outweighs benefit)
Selective estrogen receptor modulators (SERMS)
- Tamoxifen - the only approved endocrine therapy for DCIS. Reduces local recurrence but no improvement in survival
- Reduce ipsilateral & contralateral breast cancer risk.
- NSABP-B24
- Randomized patient with DCIS post BCT to TMX vs. Placebo.
- 15 years outcome:
- Local recurrence rate lower (8.5% vs. 10%)
- Lower Contralateral breast cancers (7.3% vs. 10.8%)
- Overall survival same (2.3% vs. 2.7%)
Role of AI in DCIS
Aromatase inhibitors (AI)
- Alternative totamoxifen in postmenopausal women with ER-positive DCIS.
- NSABPB-35 trial
- 3100 postmenopausal women with ER-positive post BCT
- Anastrazoleresulted in a decreased rate of breast cancer events at 10 years compared withtamoxifen but no difference in either DFS or OS rate
- Toxicities associated with aromatase inhibitors include loss of bone density, fractures, and cardiovascular risk.
- Decision for endocrine therapy should consider risk and
benefits; tamoxifen increase risk of endometrial CA and VTE while anastrozole leads to osteoporosis and risk of CVS events - Latest RCT on tamoxifen vs anastrozole showed similar
efficacy in preventing recurrence but different toxicity profile (IBIS-II and NSABP B-35)
Prognosis of DCIS
- Risk of breast cancer death is 1.9%.
- Recurrence at 10 years
- Mastectomy : risk 1%
- BCS & RT : 10%
- BCS : 30-40%
- 50% of local recurrence is IDC.
Risk factors for recurrence in DCIS
- Age < 40
- High grade , poorly differentiated
- Comedo necrosis type
- Size >2cm
- Margin width <2mm
- Presence of negative prognostic factor ↑ risk for poorly differentiated IDC
- ER / PR Negative
- HER2 Positive
- P53, Ki67 Positive
- Patient presentation - Symptomatic
DCIS in Male
- 5% of BRCA male
- Presents with retro-areolar cystic mass or bloody nipple discharge
- Main histological subtypes: Cribriform, papillary
- Management: Mastectomy or WLE + RT
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🦸🏻♀️DCIS18
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🦹🏽♀️LCIS6
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🧟♀️Paget's Disease9
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👱♀️Early Breast Ca. 💝61
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🧑🦰👨🦰Locally Advanced Breast Cancer + Male Breast Cancer7
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🧙🏻♀️Metastatic Breast Ca17
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🤶Recurrence Breast cancer7
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🧛♀️Inflammatory Breast Carcinoma (IBC)12
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🤰Breast cancer in pregnancy14
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🧝♀️Phyllodes Tumor & Fibroadenoma23
