BREAST CANCER CLINICAL SCENARIOSClinical Scenario 163 year old postmenopausal white female, G2P2, with h/o HTN, hyperlipidemia, GERD, who recently noted a lump in her right breast. Patient denies any breast pain, nipple discharge or nipple inversion bilat. On exam, there is an approximately 2.0 cm palpable lesion in upper outer quadrant. No palpable lymphadenopathy bilaterally. Former smoker (23 pk-yr). Social etoh. +FHX: M-grandmother dx’d w/ breast cancer @ 70. Mother dx’d with esophageal cancer. KPS= 90.

Work-up Imaging

Mammogram/Tomosynthesis/US= At site of palpable abnormality, there is a spiculated mass measuring 2.4 x 2.2 cm, which corresponds with ultrasound finding. No significant axillary lymphadenopathy bilat. BI-RADS 5: Highly suspicious for malignancy.

Biopsy/surgery

RT breast @ 11:00 axis, 6 FN, US-guided core biopsy:

Invasive ductal carcinoma, poorly differentiated. Suspicious for LVI. Nottingham Histologic Grade:

Tubular differentiation: 3 Nuclear pleomorphism: 3 Mitotic count: 3 Tumor grade: 9/9 Overall grade: 3

RT breast partial mastectomy @ UOQ, with sentinel lymph node bx of level 1 axillary nodes:

Histologic type: Invasive duct carcinoma. Tumor Size: 32mm Tumor Focality: Unifocal LVI: present DCIS: DCIS present. Solid & cribriform, intermediate nuclear grade with focal central necrosis. Margins: Margins for invasive ca and DCIS negative. Closest margin: 2 mm anterior. Sentinel lymph nodes examined: 2 Sentinel lymph nodes involved: 1 positive. No extranodal extension identified. Size of largest

metastatic deposit= 3 mm.

Immunohistochemistry Results: ER= 100% 3+ (Strongly positive) PR= 95% 3+ (Strongly positive) HER2 by IHC: 2+, Equivocal HER2 by FISH: Negative.

o Her2:CEP17 ratio: 1.2o Average number of Her2 signals per cell: 4.15o Average number of CEP17 signals per cell: 3.35

Ki-67= 3+ in 21%, high proliferation.

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Radiation Therapy Summary

Plan Beam Energy

Fractions Dose/fx(cGy)

Total Dose(cGy)

First txt Last txt

RT breast, axillary LNs

15X/6X 26 180 4680 5/1/18 6/5/18

RT S’clav 15X 26 180 4680 5/1/18 6/5/18Lumpectomy tumor bed boost

15 MeV 7 200 1400 6/6/18 6/14/18

Radiation therapy was administered to the breast and supraclavicular lymph nodes with a 3D- conformal plan. The boost to the lumpectomy cavity was delivered via an electron boost. The patient tolerated treatment well with only the expected mild to moderate skin erythema and patchy dry desquamation. Patient to start Anastrozole soon.

Post-surgery, patient also received ACT chemotherapy.

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Scenario 1Primary Site C50.4 MP Rule M3 Clinical Grade 3Histology 8500 H Rule H4 Pathological Grade 3Behavior 3 Post Therapy Grade

Stage Data itemsClinical Tumor Size

024 Pathological Tumor Size 032 Tumor Size Summary 032

AJCC StageClinical T cT2 Pathological T pT2 Post-therapy TcT Suffix pT Suffix pT SuffixClinical N cN0 Pathological N pN1a Post-therapy NcN Suffix pN Suffix (sn) pN SuffixClinical M cM0 Pathological M cM0 Post-therapy MClinical Stage 2A Pathological Stage 2A Post-therapy StageGrade G3 Her 2 - ER + PR + Grade G3 Her 2 - ER + PR + Grade Her 2 ER PRSummary Stage 2018 3 Regional to lymph nodesEOD Primary Tumor 100EOD Lymph Regional Nodes 200EOD Mets 00Regional Nodes Positive 01Regional Nodes Examined 02Sentinel Lymph Nodes Positive 01Sentinel Lymph Nodes Examined 02Lymphovascular Invasion 1

SSDI’sLymph Nodes Positive Axillary Level I-II 01ER Summary 1ER Percent Positive 100ER Allred Score 08PR Summary 1PR Percent Positive 095PR Allred Score 08HER2 Overall Summary 0HER2 IHC Summary 2HER2 ISH Summary 0HER2 ISH DP Ratio 1.2HER2 ISH DP Copy No 4.1HER2 ISH SP Copy No XX.9Ki-67 (MIB-1) 21.0Oncotype DX Recur Score XX9Oncotype Dx Risk Level Invasive 9Oncotype DX Recur Score - DCIS XX6Oncotype Dx Risk Level - DCIS 6Multigene Signature Method 9Multigene Signature Result 9Response Neoadjuv Therapy 0

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Radiation-Scenario 1Phase 1 Phase 2 Phase 3

Rad Primary Treatment Volume 40: whole breast 04: Breast/CW ln 41: partial breastRad Treatment Modality 02: photons 02: photons 04: electronsRadiation to Draining Lymph Nodes 04: breast/CW ln 88: NA 00: Not RT to LNsExt Beam Rad Planning Technique 04: 3D-conformal 04: 3D-conformal 01: External beam, NOSDose per Fraction 00180 00180 00200Number of Fractions 026 026 007Total Dose 004680 004680 001400# of Phases of Rad Tx to this Volume 03Rad Treatment Discontinued Early 01: RT completed as prescribedTotal Dose 999998 (See STORE, p. 336)Reason no Radiation 0: RT was administered

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Clinical Scenario 271 year-old Asian female with h/o Hashimoto thyroiditis, chronic sinusitis, who recently underwent routine screening breast imaging with abnormal findings on left breast. On breast exam, there are no discreet masses on either breast. No nipple discharge or inversion. No palpable axillary adenopathy. Patient is a former smoker (10 pk-yr). No etoh consumption and no family history of cancer.

Work-up Imaging

Left breast screening mammogram/US: No suspicious sonographic findings bilat. On mammogram, there are new suspicious clusters of pleomorphic microcalcifications in left UOQ. Biopsy recommended. BI-RADS 4: suspicious.

Biopsy/surgery

Left breast @ 9:00, 1 cm FN, mammo-guided core bx: o Ductal carcinoma in situ (DCIS), solid and cribriform patterns o Low to intermediate nuclear grade. o Calcifications present in association with DCIS and benign ducts. o ER= 100% 3+. PR= 100% 3+.

Left partial mastectomy with sentinel lymph node bx: o Histologic Type: Ductal Carcinoma In Situ (DCIS), solid and cribriform types o Tumor Size: 9mmo Grade: intermediate nuclear grade. o Extension: No invasive or microinvasive component found. No necrosis. o Lymph Nodes

0/1 sentinel lymph node negative 0/1 non-sentinel lymph node negative.

o Margins: Negative. Closest margin >5 mm.

Oncotype Dx Recurrence Score – DCIS

Recurrence score of 67 (high risk of recurrence)

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Radiation Therapy Summary

Patient received a hypofractionated accelerated regimen. The left breast received a total dose of 4256 cGy, 266 cGy in 16 fractions using 3D Field-in-Field (FinF) technique with breast tangents @ 100 SAD, using 6MV photons. This was followed by a boost to the lumpectomy cavity, consisting of 250 cGy in four fractions, 6MV, 3D-conformal for a total dose of 5256 Gy. Patient tolerated the treatment well with no treatment interruptions.

Target Volume InitialLeft Breast

Treatment PlanningImaging New CT Sim

Motion Mgmt Breath HoldModality Photon EBRTPlanning 3D

Fields TangentsEnergy/Source 6 MV

Prescribed to Isodose per planFraction & Dosing

Fraction Dose 2.66 GyFraction Number 16

Fractions/week 1 fx dailyTotal Dose 42.56 Gy

Cumulative EBRT Dose 42.56 Gy

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Medial Breast Tangent Parameters

Machine Scale Variant IECEnergy Mode 6XDose Rate 600 MU/minTechnique Static IMRTSource-axis-distance (SAD) 100.0 cmCalculated Source-skin-distance (SSD) 91.9 cmField Size 9.0 cm x 17.0 cm (X1: +2.5 cm, X2: +6.5 cm, Y1:

+7.0 cm, Y2: 10.0 cm) Asymmetric X&YGantry Rtn 300.0 degColl Rtn 10.0 degCouch Rtn 0.0 degField Normalization MethodField Normalization FactorField Weight FactorMLC Transmission factor 1.3%MU 169

Lateral Breast Tangent Parameters

Machine Scale Variant IECEnergy Mode 6XDose Rate 600 MU/minTechnique Static IMRTSource-axis-distance (SAD) 100.0 cmCalculated Source-skin-distance (SSD) 91.2 cmField Size 8.5 cm x 17.0 cm (X1: +6.0 cm, X2: +2.5 cm, Y1: +7.0

cm, Y2: 10.0 cm) Asymmetric X&YGantry Rtn 123.0 degColl Rtn 350.0 degCouch Rtn 0.0 degField Normalization MethodField Normalization FactorField Weight FactorMLC Transmission factor 1.3%MU 165

Static IMRT is another way of describing Field-in-Field technique, which is basically a 3D-Conformal plan.

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Scenario 2Primary Site C50.8 MP Rule M3 Clinical Grade MHistology 8500 H Rule H2 Pathological Grade MBehavior 2 Post Therapy Grade

Stage Data itemsClinical Tumor Size

010 Pathological Tumor Size 009 Tumor Size Summary 009

AJCC StageClinical T cTis Pathological T pTis Post-therapy TcT Suffix pT Suffix pT SuffixClinical N cN0 Pathological N pN0 Post-therapy NcN Suffix pN Suffix (sn) pN SuffixClinical M cM0 Pathological M cM0 Post-therapy MClinical Stage 0 Pathological Stage 0 Post-therapy Stage

Summary Stage 2018 0EOD Primary Tumor 000EOD Lymph Regional Nodes 070EOD Mets 00Regional Nodes Positive 00Regional Nodes Examined 02Sentinel Lymph Nodes Positive 00Sentinel Lymph Nodes Examined 01Lymphovascular Invasion 9

SSDI’sLymph Nodes Positive Axillary Level I-II X9ER Summary 1ER Percent Positive 100ER Allred Score 08PR Summary 1PR Percent Positive 100PR Allred Score 08HER2 Overall Summary 9HER2 IHC Summary 9HER2 ISH Summary 9HER2 ISH DP Ratio XX.9HER2 ISH DP Copy No XX.9HER2 ISH SP Copy No XX.9Ki-67 (MIB-1) XXX.9Oncotype DX Recur Score XX6Oncotype Dx Risk Level Invasive 6Oncotype DX Recur Score - DCIS 67Oncotype Dx Risk Level - DCIS 2Multigene Signature Method 9Multigene Signature Result X9Response Neoadjuv Therapy 0

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Radiation-Scenario 2Phase 1 Phase 2 Phase 3

Rad Primary Treatment Volume 40: Breast-whole 41: Breast-partialRad Treatment Modality 02: external

beam, photons02: external beam, photons

Radiation to Draining Lymph Nodes 00: No RT to draining LNs

00: No RT to draining LNs

Ext Beam Rad Planning Technique 04: 3D conformal 04: 3D conformalDose per Fraction 00266 00250Number of Fractions 016 004Total Dose 004256 001000# of Phases of Rad Tx to this Volume 02Rad Treatment Discontinued Early 01: RT completed as prescribedTotal Dose 005256Reason no Radiation 0: RT was administered

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Clinical Scenario 359 year-old postmenopausal Hispanic female with history of left calf malignant melanoma in 2006, status post, Mohs’ resection and immunotherapy, who underwent routine screening mammogram with suspicious findings on right breast. On exam, there are no palpable lesions on either breast. Patient denies any nipple discharge. No observable nipple retraction and no palpable axillary lymphadenopathy. Nonsmoker. Social drinker. +FHX: Mother and M-grandmother dx’d with breast cancer. Given patient’s family h/o breast cancer, pt underwent genetic testing with BRCA 1/2 negative results.

Work-up Imaging

MMG/US: Right subareolar breast nodule, 6 mm. US with same finding. MRI breast bilat: Intensely enhancing 9 mm lesion, retroareolar. No other focus of enhancement seen

on LT or RT breast. No evidence of axillary lymphadenopathy.

Biopsy/surgery

RT Breast, subareolar @ 1:00, US-guided bx: o Invasive ductal carcinoma. o Tumor grade: 8/9. o Max length in a single core= 7 mm. o DCIS, cribriform, solid, intermediate nuclear grade. o ER/PR+. HER2: 1+, NEG.

Right SAVI Scout Reflector Localized partial mastectomy with sentinel lymph node bx: o Tumor Size: 10mmo Focality: Unifocal o Histologic Type: Invasive carcinoma of no special type (NST) with lobular features.o Grade: 9/9. Overall Nottingham grade: 3. o DCIS, Solid, intermediate nuclear grade. o No clear-cut morphological evidence of lymphovascular invasion. o Sentinel Lymph Nodes= 0/1 negative. o Margins negative. Closest margin= 6 mm inf.

Immunohistochemistry Results: o ER= 3+ positive in 99%. o PR= 3+ positive in 70%o HER2: 0+, negative. o Ki-67= 3+ in 31%, high proliferation. o Luminal B subtype. o Oncotype DX Recurrence Score= 14.

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Radiation Therapy Summary

Patient underwent IORT to right breast, using the Zeiss Intrabeam XRS 50 Kv unit. Prescribed dose to the surface was 20 Gy, with a 4.0 cm applicator. Dose rate = 0.712 Gy/minute @ the surface. Treatment time = 28 minutes, 45 seconds by ionization chamber second check measurements. Ultrasound simulations confirmed that the skin to applicator distances were: 1.12 cm sup, 0.98 cm lat, 1.1 cm inf, and 0.8 cm medially, all within acceptable distances. IORT was followed by EBRT as detailed below:

Target Volume InitialRT 1:00 lumpectomy cavity

Treatment PlanningImaging Ultrasound Sim

Motion MgmtModality HDR BrachytxPlanning 2D

Fields ApplicatorEnergy/Source Electronic kV

Prescribed to Depth 0 cmFraction & Dosing

Fraction Dose 20 GyFraction Number 1

Fractions/week 1 fx dailyTotal Dose 20 Gy

Cumulative EBRT Dose 20 Gy

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Plan Beam Energy

Fractions Dose/fx(cGy)

Total Dose(cGy)

RT breast 6 MV 25 180 4500

Scenario 3Primary Site C50.1 MP Rule M3 Clinical Grade 3Histology 8500 H Rule H4 Pathological Grade 3Behavior 3 Post Therapy Grade

Stage Data itemsClinical Tumor Size

009 Pathological Tumor Size 010 Tumor Size Summary 010

AJCC StageClinical T cT1b Pathological T pT1b Post-therapy TcT Suffix pT Suffix pT SuffixClinical N cN0 Pathological N pN0 Post-therapy NcN Suffix pN Suffix (sn) pN SuffixClinical M cM0 Pathological M cM0 Post-therapy MClinical Stage 1A Pathological Stage 1A Post-therapy StageGrade G3 Her 2 - ER + PR + Grade G3 Her 2 - ER + PR + Grade Her 2 ER PRSummary Stage 2018 1-LocalizedEOD Primary Tumor 100EOD Lymph Regional Nodes 000EOD Mets 00Regional Nodes Positive 00Regional Nodes Examined 01Sentinel Lymph Nodes Positive 00Sentinel Lymph Nodes Examined 01Lymphovascular Invasion 0

SSDI’sLymph Nodes Positive Axillary Level I-II X9ER Summary 1ER Percent Positive 099ER Allred Score 08PR Summary 1PR Percent Positive 070PR Allred Score 08HER2 Overall Summary 0HER2 IHC Summary 0HER2 ISH Summary 9HER2 ISH DP Ratio XX.9HER2 ISH DP Copy No XX.9HER2 ISH SP Copy No XX.9Ki-67 (MIB-1) 31.0Oncotype DX Recur Score 014Oncotype Dx Risk Level Invasive 0Oncotype DX Recur Score - DCIS XX6Oncotype Dx Risk Level - DCIS 6Multigene Signature Method 9Multigene Signature Result X9Response Neoadjuv Therapy 0

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Radiation-Scenario 3Phase 1 Phase 2 Phase 3

Rad Primary Treatment Volume 41: Breast-partial 40: Breast-wholeRad Treatment Modality 02: external

beam, photons02: external beam, photons

Radiation to Draining Lymph Nodes 00: No RT to draining LNs.

00: No RT to draining LNs.

Ext Beam Rad Planning Technique 12: Electronic brachytherapy

04: 3D-conformal

Dose per Fraction 002000 00180Number of Fractions 001 025Total Dose 002000 004500# of Phases of Rad Tx to this Volume 02Rad Treatment Discontinued Early 01: RT completed as prescribedTotal Dose 006500Reason no Radiation 0: RT was administered

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Clinical Scenario 4

55-year-old W/F, who on routine screening breast imaging had abnormal findings on LT breast. Patient is asymptomatic, denies any breast masses bilat. No nipple retraction or discharge. On exam, no palpable adenopathy on right/left axilla. Non-smoker. Social alcohol use. No family hx of cancer.

Work-up Imaging

Bilateral screening mmg/US= New grouped pleomorphic calcifications on left breast @ 1:00.

Unilateral LT breast mmg/US callback= In left breast @ 1:00 axis, there are grouped pleomorphic calcifications spanning about 8 mm. BI-RADS 4: suspicious.

Biopsy/surgery

Left breast @ 1:00 axis, 3FN, US-guided core bx= DCIS, solid type, low nuclear grade. Largest dimension in a single core= 8 mm.

Left breast SAVI Scout localizer partial mastectomy with sentinel lymph node bx

0.9 cm DCIS, solid & cribriform, low nuclear grade. No invasive component present. SLNs= 0/2 neg Margins negative. Closest margin @ 3 mm lat. Stage pTis, pN0 (sn).

Immunohistochemistry Results: ER= 3+ positive in 90%. PR= 3+ positive in 85%.

Radiation Therapy Summary

Using a 6-1 mini SAVI catheter, the lumpectomy cavity received 34 Gy in 10 treatments, BID.

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Scenario 4Primary Site C50.4 MP Rule M3 Clinical Grade LHistology 8500 H Rule H2 Pathological Grade LBehavior 2 Post Therapy Grade

Stage Data itemsClinical Tumor Size

008 Pathological Tumor Size 009 Tumor Size Summary 009

AJCC StageClinical T cTis Pathological T pTis Post-therapy TcT Suffix pT Suffix pT SuffixClinical N cN0 Pathological N pN0 Post-therapy NcN Suffix pN Suffix (sn) pN SuffixClinical M cM0 Pathological M cM0 Post-therapy MClinical Stage 0 Pathological Stage 0 Post-therapy Stage

Summary Stage 2018 0 In SituEOD Primary Tumor 000EOD Lymph Regional Nodes 070EOD Mets 00Regional Nodes Positive 00Regional Nodes Examined 02Sentinel Lymph Nodes Positive 00Sentinel Lymph Nodes Examined 01Lymphovascular Invasion 9

SSDI’sLymph Nodes Positive Axillary Level I-II X9ER Summary 1ER Percent Positive 090ER Allred Score 08PR Summary 1PR Percent Positive 085PR Allred Score 08HER2 Overall Summary 9HER2 IHC Summary 9HER2 ISH Summary 9HER2 ISH DP Ratio XX.9HER2 ISH DP Copy No XX.9HER2 ISH SP Copy No XX.9Ki-67 (MIB-1) XXX.9Oncotype DX Recur Score XX6Oncotype Dx Risk Level Invasive 6Oncotype DX Recur Score - DCIS XX9Oncotype Dx Risk Level - DCIS 9Multigene Signature Method 9Multigene Signature Result X9Response Neoadjuv Therapy 0

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RadiationPhase 1 Phase 2 Phase 3

Rad Primary Treatment Volume 41: Breast-partialRad Treatment Modality 09:

Brachytherapy, intracavitary, HDR

Radiation to Draining Lymph Nodes 00: No RT to draining LNs

Ext Beam Rad Planning Technique 88: Treatment not by external beam

Dose per Fraction 99998Number of Fractions 010Total Dose 999998# of Phases of Rad Tx to this Volume 01Rad Treatment Discontinued Early 01: RT completed as prescribedTotal Dose 999998Reason no Radiation 0: RT was administered

NCCN Guidelines-Invasive Breast Cancerv3.2018

• Whole Breast RT • 45-50.4 Gy in 25-28 fractions (fx), or • 40-402.5 Gy in 15-16 fx (hypofractionation preferred),• Treatments 5 days/wk,• Tumor bed boost recommended in patients with high risk features

• Chest Wall(CW) RT • 45-50.4 Gy in 25-28 fx to CW +/- scar boost @ 1.8-2 Gy/fx for total of about 60 Gy.

• Regional Nodal RT • 46-60 Gy, 23-25 fx, 5 days/wk

• Accelerated Partial Breast Irradiation (APBI) • 34 Gy in 10 fx, twice a day (BID), via brachytherapy, or • 38.5 Gy in 10 fx, BID, with EBRT• Tumor bed boost recommended in patients with high risk features

• APBI patient selection criteria: • 50 years or older, with invasive ductal ca,• T1 disease with negative margin width ≥ 2 mm, no LVI, ER+, BRCA-, or• Low/intermediate nuclear grade, screening detected DCIS, ≤ 2.5 mm, negative margins ≥ 3

mm

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