Clinical Case Discussions

Rad Onc

Surgeon

Surgeon

Surgeon

Med Onc Med Onc

Med Onc

Med Onc

Med Onc

Pathologist

16:20 - 18:00

31 y.o-female, 5 months before her wedding

she noticed a nodule in the axillary extension

of the R breast.

PMHx: none

Fam Hx: no cancer

Case #1

Dec 1st, 2018

2.4cm nodule in the

axillary extension of

the right breast.

Microcalcifications.

Atypical LN in R axilla

Core Bx:

IC NOS, HG3, no LVI, no DCIS

ER 10%, Allred 5

PR 50%, Allred 7

Her2+++

Ki67 40%

FNA of R axillary LN: + malignant cells

Genetic panel (Invitae): VUS in

FANCM(NM_020937.2):c.853A>G(p.Lys285Glu).

No distant

metastasis

What would you expect as local treatment after neoadjuvant therapy?

1. Breast conserving surgery + mandatory ALND followed by XRT including axilla, supra clav. fossae, int. mammary LNs

2. Bilateral adenomastectomies + mandatory ALND followed by XRT including axilla, supra clav. fossae, int. mammary LNs

3. Bilateral adenomastectomies + ALND only if SLNBx+, followed by XRT to SCF and Int Mammary LNs

4. Breast conserving surgery + ALND only if SLNBx+, followed by XRT to breast, axilla, SCF and int mammary LNs

5. Some other option

Question #1 (please vote):

Surgeons:

• what do you plan regarding the breast and axilla? Will thischange if you have a complete clinical response (including MRI)?

Rad Onc:

• will your RT plan change depending on pathological response?

Study Treatment pCR em RH+ pCR em RH-

NeoSphere Pertuzumab/Trastuzumab 26% 63%

TRYPHAENA Pertuzumab/Trastuzumab 46/50% 65-84%

TRAIN2 Pertuzumab/Trastuzumab 51/55% 84-89%

KRISTINE Pertuzumab/Trastuzumab 46% 71%

31, IC G3, HR+, Her2+++, cT2 cN1 M0

Med Onc:

• Which neoadjuvant regimen and why?

• What if cN0? Would you still start with neoadjuvant

therapy?

• Fertility preservation: how many weeks can you wait?

• Retrieved 15 oocytes >> peritonitis (ascitis, pain) >> 3 weeks for

resolution

• She received TCHP (Taxotere+Carboplatin+Herceptin+Pertuzumab) x6

(and LHRH analog for ovarian function preservation)

• Breast nodule and LN no longer palpable

• Surgeons:

• Do you repeat a pre-op MRI or PET-CT? Does it change your surgical

plan?

31, IC G3, HR+, Her2+++, cT2 cN1 M0

April 29th, 2019Dec 1st, 2018

Complete

clinical

response

May 14th, 2019: bilateral skin/nipple sparing mastectomies (per patient)+ R LND

(surgeon felt that LNs were macroscopically suspicious)

31 yo, IC G3, HR+, Her2+++, cT2 cN1 M0

Neoadjuvant TCHP x6 with complete clinical

respose

Bilateral skin/nipple sparing mastectomies + R

LND (LNs were macroscopically suspicious)

Pathology Report:

no residual tumor (either invasive or in situ)

0/27 LN

RCB 0

Surgeons:

• What is your opinion regarding RT now? What is the risk of

lymphedema?

Rad Onc:

• What is your opinion regarding RT now?

Pathology:

• Can treatment change IHQ results in the residual tumor

(i.e Her2+ > Her2-)?

• Is reporting RCB the standard? How long does it take to fully

evaluate RCB?

Heather NeumanIsabelle Bedrosian

E. Mamounas Reshma Jagsi

ALND should remain standard of care in ALL patients

who are node positive prior to neoadjuvante

chemotherapy until...• We have a minimally axillary staging approach that:

• Is highly accurate, ie low FNR• Established through porspective, multi-institutional studies

• Accounts for tumor burden/tumor biology

• The FNR has established acceptable long term oncologic safety (ie LRR)

• Does not impair decisions regarding adjuvante systemic therapy that may affect survival

• We have considered potential therapeutic role of

axillary surgery in chemoresistant disease

Conclusion• Complete ALND is NOT indicated for all patiets with

+ nodes prior to NAST

• LOW risk of “missing something”

• SLN mapping with dual dye

• Removal of the clipped node

• Removal of ≥ 2lymph nodes

• Consequences of “missing something” in the setting

of adjuvante radiation are likely low

• Can spare up to 50% of women a morbid,

oncologically unnecessary procedure

SLNB Alone is Appropriate in Pts with (+)

Axillary Nodes before NAC

If you Do the Following:

• Appropriaes candidate selection (T1-3, N1)

• Dual agente mapping (isotope + dye)

• identification and removal of > 2 (-) SLNs

• Clip placement in the positive node with localization

and retrieval of (-) clupped node

• Considerations of performing IHC in the SLN and

completing ALND even with N0i+ disease

Conclusions

• When a patient has had complete ALND and no

disease is remaining in the axilla, cartainly no

directed RT to levels I and II is indicated

• Whether treatment to the other regional nodal

basins can be omitted will ultimately have to

await a definitive aswer from the large ongoing

NRG trial

• In the meantime, eligible patients shoould be

encouraged to enroll on the trial

Question #2 (please vote)

Regarding adjuvant therapy, what would yo do?

1. Finish 1 year of Trastuzumab and Pertuzumab, start AI continue LHRH

analog

2. Finish 1 year of Trast/Pert, start Tamoxifen and discontinue LHRH

analog

3. Finish 1 year of Trast/Pert, start Tamoxifen and continue LHRH analog

4. Finish 1 year of Trastuzumab, start Tamoxifen and continue LHRH

analog

5. Finish 1 year of Trastuzumab, start Tamoxifen and discontinue LHRH

analog

31 yo, IC G3, HR+, Her2+++, cT2 cN1 M0 >> TCHPx6>> pCR

Med Onc:• Continue Trastuzumab to finish 1 year ?

• Continue Trastuzumab and Pertuzumab

to finish 1 year?

• What if it was RCB1-3?

• Continue aLHRH + start na AI? Comment

on estradiol

• Continue aLHRH + start Tam?

• Tam only?

KATHERINE

KRISTINE

NeoSphere

TRYPHAENA

FEC q3w x 3

Herceptin q3w cycles 5-17

FEC q3w x 3

Herceptin q3w cycles 5-17

Docetaxel q3w x 4 → FEC q3w x 3

Herceptin q3w cycles 5-17

FEC q3w x 3

Herceptin q3w cycles 5-21

S

U

R

G

E

R

Y

SURGERY

Trastuzumab

to complete

1 year

T-DM1

3.6 mg/kg IV Q3W

14 cycles

Trastuzumab

6 mg/kg IV Q3W

14 cycles

R

1:1

N = 1486

S

U

R

G

E

R

Y

Trastuzumab

Pertuzumab

T-DM1

Pertuzumab

12 cycles of adjuvante

HER2-therapy

Case #2

36 year old, no PMX

Patient felt a lump in R breast

US and MMG: 1.4cm nodule at JUQ, axillary LN suspicious

Fam Hx: 2 children, Hx of breast and ovarian cancer (mat aunt / grandmother)

3/18/2019: Core Bx: IC NOS, G3, no LVI,

ER-, PR-, Her2-, Ki67 25%

Lymphocyte Infiltration 20%

FNA axillary LN: + for malignant cells

36 yo, IC NOS, G3, TN, cT1c cN1 M0

PET-CT: no evidence of metastatic diseaseInvitae – negative for pathogenic mutations

How should this patient be treated?

1. Neoadjuvant therapy with anthracycline and taxane, carboplatin,

followed by BCS surgery and ALND > Capecitabine if RCB1-3, XRT per

clinical stage

2. Neoadjuvant therapy with anthracycline and taxane, followed by

BCS surgery and ALND only if SLN+ > Capecitabine if RCB1-3, XRT per

clinical stage

3. Neoadjuvant therapy with anthracycline and taxane, carboplatin,

followed by surgery (decision after genetic panel) and ALND >

Capecitabine if RCB1-3, XRT adapted depending on the RCB

4. Some other option

Question #1 (please vote)

Pathology:What is the value of reporting Lymphocyte Infiltration in

2019?

Surgeons:For TNBC, what is your threshold to indicate neoadjuvant

therapy rather than surgery upfront?

Surgeons in audience: raise hands those who clip +LNYoung women with significant fam hx but negative for

genetic testing, what do you recommend?

Med OncNeoadjuvant chemo:

Do we agree about Carbo/Paclitaxel >> ddAC for every

TNBC?

What if BRCA mutation?

What if BRCA mutation with HR+?

• Is a genetic predisposition panel always necessary, or

BRCA enough?

After 12 weeks of Carbo AUC 1.5/Paclitaxel 80 mg/m2

Complete

readiologic

response in breast

and axilla

MedOnc:Patient asks if she can be operated now and only receive ddAC

if RCB1-3

Case #3

43 yo premenopausal patient

• June 2018, patient noticed a lump in her left breast, with progressive

enlargement. Also, she noticed a palpable ipsilateral axillary lymph node.

• Clinical Staging cT2cN1

• October/2018: Left breast biopsy revealed an Invasive Ductal Carcinoma • Grade II, ER+ 100%, PR +100%, HER2 negative, Ki67 + 10%

• Pathology Review confirmed these results

• Fine needle aspiration of axillary LN: + for malignant cells

• Initial PET CT revealed a suspicious nodule in her liver

• Liver biopsy confirmed metastatic lesion

• Pathology result: Infiltrating carcinoma in the liver from breast origin : RE+, Mamoglobin +,

GATA-3 +, HER2 negative

How would you treat this patient?

1. LHRHa + AI + Fulvestrant

2. LHRHa + AI or Tam + any CDK4/6i

3. LHRHa + AI or Tam + Ribociclib necessarily (based on MONALEESA 7)

4. Chemotherapy until response in liver, then LHRHa+ HT

5. Some other option

Question #1 (please vote)

Clinical Staging cT2cN1M1 (oligometastatic)GH II IDC ER+ 100% PR +100% HER2 negative Ki67 + 10%

Med Oncs: What would you do now?

• Recommend hormone therapy? Which one? Combination?

• Recommend CDKi plus endocrine therapy. Which CDKi and

which HT?

• Recommend cytotoxic chemotherapy?

Premenopausal patient, 43 years old

Clinical Staging cT2cN1M1GH II IDC ER+ 100% PR +100% HER2 negative Ki67 + 10%

Single liver met (biopsy proven)

Med Oncs:

• Would you request any invasive procedure (liver, breast, axilla)?

Surgeons:

• Would you perform clipping of the tumor in the breast and/or theaxilla?

• Would you proceed differently if this were a Her2+ MBC?

Premenopausal patient, 43 years old

GH II IDC ER+ 100% PR +100% HER2 negative Ki67 + 10%Single liver met (biopsy proven)

• Patient was started on goserelin q28 days, letrozole and

palbociclib, with excellent tolerability and minor impact

on her quality of life.

• No dose reductions were necessary

Premenopausal patient, 43 years old

before

after

1. Continue systemic therapy only.

2. Proceed with BCS + ALND + XRT + follow liver lesion

3. Proceed with BCS + ALND + XRT with curative intent +

SBRT to liver lesion + “adjuvant chemo” with curative

intent

4. Some other option

What now?

Question #2 (please vote)

Patient underwent BCS + ALND and SBRT to single liver lesion:

Path: Residual IC NOS with signs of partial response

Grade I

Size: 1.5x1.0cm

ALND: 5/26 +LN, largest 2.8mm, no extracapsular

extension, signs of tumor regression in 2LN

Case #4

61-year-old female is referred after undergoing breast surgery for a cancer:

Screening MMG with a 2.6cm nodule in RUQ, with microcalcifications

PMHx: HTN, obesity, took HRT for 5 years (51-56)

Fam Hx: no cancer, 3 daughters

Physical Exam: palpable nodule in RUQ R breast, no palpable LN,

Core Bx: IC NOS, Grade 2, with high grade DCIS 20%, no LVI,

ER 90% Allred 8, PR 20% Allred 6, HER-2 negative, Ki67 20%

BCS + SNLBx: IC NOS, 2.5cm, high grade DCIS in <20%, negative margins, no LVI

1/3 SL with micrometastasis (1.7mm), with extracapsular extension of

0.7 mm

pT2 pN1(mi) M0, HR+, HER2 neg

Mammaprint: low risk (brace for tomorrow)

61, BCS + SLBx: IC NOS, 2.5cm, high grade DCIS in <20%, negative margins, no LVI, 1/3 SL+ for

micrometastasis, with extracapsular extension; pT2 pN1(mi) M0, HR+, Her2-, Ki67 25%

Mammaprint: low risk

• Surgeons: implications of micromets and

extracapsular extension in the axilla?

• RadOnc: When is hypofractionation indicated in

2019? Contraindications? Does intrinsic subtype or

risk group change XRT plan in 2019?

• MedOnc/Pathology:

• Do we agree that she needs NO chemo and NO

other signature?

• HT for a total of 5 years? 7 years? 10 years?

• Do you use CTS5 to decide duration? BCI?

Prosigna?