Neoadjuvant therapy for Neoadjuvant therapy for breast cancer: the Stoddard breast cancer: the Stoddard

protocolprotocol

Scott D. Hamling, MDScott D. Hamling, MD

General SurgeonGeneral Surgeon

The Iowa ClinicThe Iowa Clinic

ObjectivesObjectives

• Patient eligibilityPatient eligibility• Pretherapy evaluationPretherapy evaluation• Neoadjuvant systemic therapy Neoadjuvant systemic therapy

(NAST) options(NAST) options• Treatment response monitoringTreatment response monitoring• Definitive surgical therapyDefinitive surgical therapy• ResultsResults• The Stoddard protocolThe Stoddard protocol

Multidisciplinary Team Approach

Cases Cases

• 48yo, cT4d cN2 cM0, grade 3, IDC, -, -, +.48yo, cT4d cN2 cM0, grade 3, IDC, -, -, +.

• 60yo, cT3 cN1 cM0, grade 2, ILC, +, +, -.60yo, cT3 cN1 cM0, grade 2, ILC, +, +, -.

• 39yo, cT2 cN0 cM0, grade 2, IDC, -, -, +.39yo, cT2 cN0 cM0, grade 2, IDC, -, -, +.

• 37 yo, cT1c cN0 cM0, grade 3, IDC, -, -, -.37 yo, cT1c cN0 cM0, grade 3, IDC, -, -, -.

• 65 yo, cT3 cN0 cM0, grade 1, IDC, +, +, -.65 yo, cT3 cN0 cM0, grade 1, IDC, +, +, -.

• Who would you offer NAST to?Who would you offer NAST to?

48yo, cT4d cN2 cM0, grade 3, 48yo, cT4d cN2 cM0, grade 3, IDC, ER-, PR-, Her 2+.IDC, ER-, PR-, Her 2+.

60yo, cT3 cN1 cM0, grade 2, 60yo, cT3 cN1 cM0, grade 2, ILC, ER+, PR+, Her 2-.ILC, ER+, PR+, Her 2-.

39yo, cT2 cN0 cM0, grade 2, 39yo, cT2 cN0 cM0, grade 2, IDC, ER-, PR-, Her 2 +.IDC, ER-, PR-, Her 2 +.

37 yo, cT1c cN0 cM0, grade 3, IDC, 37 yo, cT1c cN0 cM0, grade 3, IDC, ER-, PR-, Her 2-.ER-, PR-, Her 2-.

65 yo, cT2 cN0 cM0, grade 1, 65 yo, cT2 cN0 cM0, grade 1, IDC, ER+, PR+, Her 2-.IDC, ER+, PR+, Her 2-.

NAST utilization: Stoddard NAST utilization: Stoddard registry resultsregistry results

• 2013: 15/52 (29%) patients with 2013: 15/52 (29%) patients with IBC/LABC were clearly documented as IBC/LABC were clearly documented as having been offered/given NASThaving been offered/given NAST– Most patients went straight to mastectomyMost patients went straight to mastectomy

• 2013: 1/14 (7.1%) patients had 2013: 1/14 (7.1%) patients had appropriate biospies, documented appropriate biospies, documented complete pretherapy staging, and complete pretherapy staging, and routine image monitoring during NASTroutine image monitoring during NAST

NAST rationalNAST rational

• Systemic therapy intended to reduce the Systemic therapy intended to reduce the risk of distant disease recurrencerisk of distant disease recurrence

• Improve surgical outcome when a Improve surgical outcome when a primary surgical resection is not possible primary surgical resection is not possible or the extent of resection is undersirableor the extent of resection is undersirable

• Allows in vivo treatment sensitivity Allows in vivo treatment sensitivity assessmentassessment

• Novel research windowNovel research window

Historical perspectiveHistorical perspective

• Preoperative chemotherapy historically Preoperative chemotherapy historically given to patients with inflammatory and given to patients with inflammatory and noninflammatory unresectable LABC.noninflammatory unresectable LABC.

• To summarize large and muture literature, To summarize large and muture literature, preoperative chemotherapy: (B-18, B-27)preoperative chemotherapy: (B-18, B-27)– Capable of shrinking large primary tumors Capable of shrinking large primary tumors

renduring many inoperable patients operable renduring many inoperable patients operable – Improves the survival of patients with IBC as Improves the survival of patients with IBC as

part of multimodality therapy, compared to part of multimodality therapy, compared to locoregional therapy alonelocoregional therapy alone

– Equivalent survival in operable breast cancer, Equivalent survival in operable breast cancer, compared to adjuvant chemotherapycompared to adjuvant chemotherapy

Contemporary perspectiveContemporary perspective

• Can NAST improve surgical outcomes in Can NAST improve surgical outcomes in patients with operable breast cancer?patients with operable breast cancer?– Increased rate of BCTIncreased rate of BCT– Decreased extent of axillary surgeryDecreased extent of axillary surgery

• Can NAST allow tailored therapy to Can NAST allow tailored therapy to avoid toxicities of ineffective therapy?avoid toxicities of ineffective therapy?– Biologic monitoring of new drugsBiologic monitoring of new drugs– Neoadjuvant trials to avoid adjuvant trialsNeoadjuvant trials to avoid adjuvant trials

• Is NAST optimal for all patients?Is NAST optimal for all patients?

Patient eligibilityPatient eligibility

• Surgical eligibilitySurgical eligibility– Unresectable disease: locally advanced Unresectable disease: locally advanced

breast cancer (LABC), inflammatory breast cancer (LABC), inflammatory breast cancer (IBC)breast cancer (IBC)

– Resectable disease: if BCT is not Resectable disease: if BCT is not possible or cosmetic result is possible or cosmetic result is undesirableundesirable

– Contraindication to surgery at the time Contraindication to surgery at the time of diagnosis: gestational breast cancerof diagnosis: gestational breast cancer

Patient eligibilityPatient eligibility

• Tumor biology: NAST is most Tumor biology: NAST is most appropriate in patients predicted to appropriate in patients predicted to have a good responsehave a good response– Triple-negative breast cancer (TNBC)Triple-negative breast cancer (TNBC)– Her 2 positive breast cancerHer 2 positive breast cancer

Tumor biologyTumor biology

• TNBC:TNBC:– Pathologic complete response rate with Pathologic complete response rate with

NAST 27-45%, compared to 10% for HR NAST 27-45%, compared to 10% for HR pos, Her 2 neg breast cancer (Carey, pos, Her 2 neg breast cancer (Carey, 2007) (Esserman, 2012)2007) (Esserman, 2012)

– Residual disease burden is predictive of Residual disease burden is predictive of early distant recurrence and lower early distant recurrence and lower overall survival (Liedtke, 2008)overall survival (Liedtke, 2008)

Tumor biologyTumor biology

• Her 2 positive breast cancerHer 2 positive breast cancer– I-SPY 1 trial (2012): T I-SPY 1 trial (2012): T >> 3cm, looked at pCR and 3cm, looked at pCR and

receptor status associationsreceptor status associations• Relatively high pCR of 39% following treatment with Relatively high pCR of 39% following treatment with

neoadjuvant chemotherapy (NACT) in Her 2 pos patients, neoadjuvant chemotherapy (NACT) in Her 2 pos patients, vs 18% for Her 2 neg patients.vs 18% for Her 2 neg patients.

• Relatively high pCR rate regardless of HR status Relatively high pCR rate regardless of HR status – HR pos, Her 2 pos: pCR of 33%HR pos, Her 2 pos: pCR of 33%– HR neg, Her 2 pos: pCR of 45%HR neg, Her 2 pos: pCR of 45%

• Significant increase in pCR to 60% in patients who also Significant increase in pCR to 60% in patients who also received adjuvant Her 2 directed therapy.received adjuvant Her 2 directed therapy.

– TECHNO trial (2011): Her 2 + patients receiving TECHNO trial (2011): Her 2 + patients receiving NACT + traztusumab NACT + traztusumab • pCR rate was associated with improved disease free pCR rate was associated with improved disease free

survival (DFS) and overall survival (OS)survival (DFS) and overall survival (OS)

Pretherapy evaluationPretherapy evaluation

• Complete histopathologic diagnosisComplete histopathologic diagnosis

• Initial staging evaluation to rule out Initial staging evaluation to rule out distant metastatic diseasedistant metastatic disease

• Primary tumor evaluationPrimary tumor evaluation

• Nodal evaluationNodal evaluation

Diagnosis Diagnosis

• Pathologic evaluationPathologic evaluation– Comprehensive histopathologic Comprehensive histopathologic

confirmationconfirmation– Hormone receptor status (ER/PR)Hormone receptor status (ER/PR)– Human epidermal growth factor Human epidermal growth factor

receptor 2 status (Her 2)receptor 2 status (Her 2)

Complete clinical stagingComplete clinical staging

• Comprehensive clinical staging prior Comprehensive clinical staging prior to NAST, as surgical pathologic stage to NAST, as surgical pathologic stage in expected to be alteredin expected to be altered– ExamExam– Regional imaging and biopsiesRegional imaging and biopsies– May include systemic scans to detect May include systemic scans to detect

occult distant disease, which would alter occult distant disease, which would alter surgical planning surgical planning

Primary tumor evaluationPrimary tumor evaluation

• Requires accurate radiopaque clip Requires accurate radiopaque clip placement to mark the tumor locationplacement to mark the tumor location

• Tumor size documentationTumor size documentation– ExamExam– ImagingImaging

•MammogramMammogram

•USUS

•MRIMRI

Nodal evaluationNodal evaluation

• Negative axillary examNegative axillary exam– Axillary US with core needle biopsy Axillary US with core needle biopsy

(including clip placement) of suspicious (including clip placement) of suspicious nodes detected during imagingnodes detected during imaging

– SLN bx pretherapySLN bx pretherapy•although posttherapy N stage has greater although posttherapy N stage has greater

prognostic significanceprognostic significance

Nodal evaluationNodal evaluation

• Positive axillary examPositive axillary exam– US core biopsy preferred US core biopsy preferred – Palpation FNA/core biopsyPalpation FNA/core biopsy

•Consider SLN bx if discordant pathologic and Consider SLN bx if discordant pathologic and clinical resultsclinical results

– Clip placement is advised (esp if Clip placement is advised (esp if posttherapy SLN bx is planned)posttherapy SLN bx is planned)

NAST NAST

• OptionsOptions– Neoadjuvant chemotherapy (NACT)Neoadjuvant chemotherapy (NACT)– NACT with the incorporation of biologic NACT with the incorporation of biologic

therapy (NACT + Her 2 directed therapy)therapy (NACT + Her 2 directed therapy)– Neoadjuvant hormonal therapy (NAHT)Neoadjuvant hormonal therapy (NAHT)

•Limited data regarding the use of NAHT Limited data regarding the use of NAHT compared to NACTcompared to NACT

•NACT generally offered preferentially NACT generally offered preferentially

– Recommendations based on tumor biologyRecommendations based on tumor biology

NACTNACT

• Patients receiving NACT have a Patients receiving NACT have a statistically higher likelihood of undergoing statistically higher likelihood of undergoing cosmetically desirable surgery (B-18, 27)cosmetically desirable surgery (B-18, 27)

• DFS and OS are equivalent, compared to DFS and OS are equivalent, compared to adjuvant systemic chemotherapy (B-18, adjuvant systemic chemotherapy (B-18, 27)27)– However, patients with a pCR at surgery have However, patients with a pCR at surgery have

a significant improvement in both DFS and OS, a significant improvement in both DFS and OS, compared to those with residual invasive compared to those with residual invasive diseasedisease

NACTNACT

• Regimen: Regimen: – Choice of systemic therapy is based on Choice of systemic therapy is based on

tumor biology with similar efficacy expected tumor biology with similar efficacy expected to that seen in the adjuvant setting.to that seen in the adjuvant setting.

• Timing:Timing:– Since downstaging is the primary goal of Since downstaging is the primary goal of

NAST, all planned NACT should be NAST, all planned NACT should be administered prior to surgery.administered prior to surgery.•Provided no evidence of disease progressionProvided no evidence of disease progression

NACTNACT

• Anthracycline-taxane based regimens:Anthracycline-taxane based regimens:– Multiple studies have demonstrated Multiple studies have demonstrated

increased response rates in the neoadjuvant increased response rates in the neoadjuvant setting, compared with non-taxane-setting, compared with non-taxane-containing regimen (ex. NSABP B-27)containing regimen (ex. NSABP B-27)

– ACTACT– TC if contraindication to anthracyclineTC if contraindication to anthracycline– May see carboplatin added to TNBC: May see carboplatin added to TNBC:

(GeparSixto, CALGB 40603, I-SPY 2)(GeparSixto, CALGB 40603, I-SPY 2)

NACT + Her 2 directed NACT + Her 2 directed therapytherapy• Patients with Her 2 pos cancers have a Patients with Her 2 pos cancers have a

relatively high rate of pCR with NACT (I-relatively high rate of pCR with NACT (I-SPY 1)SPY 1)

• pCR increases with the addition of Her 2 pCR increases with the addition of Her 2 directed therapy, esp if HR neg (I-SPY 2)directed therapy, esp if HR neg (I-SPY 2)

• pCR after NACT plus Her 2 directed pCR after NACT plus Her 2 directed therapy is assoc. with recurrence and therapy is assoc. with recurrence and survival advantages (TECHNO)survival advantages (TECHNO)

NACT + trastuzumabNACT + trastuzumab

• Benefit of adding Her 2 directed Benefit of adding Her 2 directed therapy (NOAH trial):therapy (NOAH trial):– Improvement in pCR rate to 43% vs 20%Improvement in pCR rate to 43% vs 20%– Reduction in relapse rate to 26% vs 39%Reduction in relapse rate to 26% vs 39%– Trend to lower mortality rate of 13% vs Trend to lower mortality rate of 13% vs

20% 20% – Increased benefit in both event free Increased benefit in both event free

survival and overall survival at 5 years survival and overall survival at 5 years compared to NACT alone.compared to NACT alone.

NACT + trastuzumab + NACT + trastuzumab + pertuzumabpertuzumab

• Pertuzumab (Perjeta)Pertuzumab (Perjeta)– Monoclonal antibody that inhibits the Monoclonal antibody that inhibits the

dimerization of Her 2 with other Her dimerization of Her 2 with other Her receptorsreceptors

– Designed to overcome trastuzumab Designed to overcome trastuzumab resistance caused by the formation of Her resistance caused by the formation of Her 2:Her 3 heterodimers.2:Her 3 heterodimers.

– NeoSphere and TRYPHAENA trials:NeoSphere and TRYPHAENA trials:• Increased pCR with addition of pertuzumab to Increased pCR with addition of pertuzumab to

trastuzumabtrastuzumab

Neoadjuvant hormonal Neoadjuvant hormonal therapytherapy• Limited data in premenopausal womenLimited data in premenopausal women• Often restricted to postmenopausal patients Often restricted to postmenopausal patients

not fit to receive or refuse NACTnot fit to receive or refuse NACT• Comparing NACT and NAHT(AI) in Comparing NACT and NAHT(AI) in

postmenopausal stage II-III HR pos cancer postmenopausal stage II-III HR pos cancer (Semiglazov et al, 2007):(Semiglazov et al, 2007):– No differences in response rates No differences in response rates – Similar median time to observed response (57 vs Similar median time to observed response (57 vs

51 days)51 days)– Similar pCR (3 vs 6%)Similar pCR (3 vs 6%)– Increased BCT rate with AI (33%) vs NACT (24%)Increased BCT rate with AI (33%) vs NACT (24%)

GEICAM studyGEICAM study

– Randomized HR + cancers to NACT vs 24 Randomized HR + cancers to NACT vs 24 weeks of exemestane (plus luteinizing-weeks of exemestane (plus luteinizing-hormone-releasing hormone analog goserelin hormone-releasing hormone analog goserelin every 4 weeks in premenopausal patients)every 4 weeks in premenopausal patients)•NACT patients had higher clinical response (66 vs NACT patients had higher clinical response (66 vs

48%)48%)

•pCR in 3 NACT patients, no pCR in NAHTpCR in 3 NACT patients, no pCR in NAHT

•Higher rate of BCT with NAHT (56 vs 47%)Higher rate of BCT with NAHT (56 vs 47%)

•Lower grade 3 and 4 toxicities with NAHT (9 vs Lower grade 3 and 4 toxicities with NAHT (9 vs 47%)47%)

NAHT drug of choiceNAHT drug of choice

• Postmenopausal patients: AI > TAMPostmenopausal patients: AI > TAM– Letrozole vs tam: significantly higher overall Letrozole vs tam: significantly higher overall

response rate (55 vs 36%) and BCT rate (45 response rate (55 vs 36%) and BCT rate (45 vs 35%) (Ellis, 2007)vs 35%) (Ellis, 2007)

– PROACT study (Cataliotti, 2006): PROACT study (Cataliotti, 2006): anastrozole vs tam; no significant difference anastrozole vs tam; no significant difference in overall response rate (40 vs 35%), in overall response rate (40 vs 35%), improved surgical option rate (43% vs 31%)improved surgical option rate (43% vs 31%)

• No preferred AI : (ACOSOG) Z1031 trialNo preferred AI : (ACOSOG) Z1031 trial– Exemestane, letrozole, anastrozole Exemestane, letrozole, anastrozole

Duration of NAHTDuration of NAHT

• Should be individualized to patientsShould be individualized to patients

• Response to therapy may not be evident Response to therapy may not be evident for 3 to 4 months and maximal response for 3 to 4 months and maximal response may take longermay take longer– Strobel et al (2008) found 62% response Strobel et al (2008) found 62% response

rate by 4 months with AI for T2 or larger rate by 4 months with AI for T2 or larger tumorstumors

• Monitoring response to therapy to guide Monitoring response to therapy to guide surgical timingsurgical timing

Treatment response Treatment response monitoringmonitoring• No formal guidelines existNo formal guidelines exist• NACT patients: exam prior to each NACT patients: exam prior to each

cycle of treatmentcycle of treatment• NAHT patients: exam every 4-8 weeksNAHT patients: exam every 4-8 weeks• Imaging: Imaging:

– Midpoint of NAST and surgical schedulingMidpoint of NAST and surgical scheduling– If disease progression suspectedIf disease progression suspected– MRI vs US depending on tumor and surgical MRI vs US depending on tumor and surgical

planplan

Tumor monitoringTumor monitoring

• MRI: (Yuan, 2010)MRI: (Yuan, 2010)– highest specificity (91%) to predict pCR, highest specificity (91%) to predict pCR,

sensitivity low (63%)sensitivity low (63%)– Sensitivity hampered by DCIS findingsSensitivity hampered by DCIS findings

• Chagpar, 2006: Chagpar, 2006: – Accuracy of exam 66%, mammo 70%, Accuracy of exam 66%, mammo 70%,

US 75%US 75%

Response monitoringResponse monitoring

• Correlation between tumor Correlation between tumor measurements by PE, imaging, and final measurements by PE, imaging, and final pathology are modest at bestpathology are modest at best

• Lack of concordance likely due to Lack of concordance likely due to variable patterns of tumor responsevariable patterns of tumor response– Symmetric shrinkage around a residual Symmetric shrinkage around a residual

fibrotic scar vs residual cancer corefibrotic scar vs residual cancer core– Complete mass resolution despite the Complete mass resolution despite the

persistence of microscopic focipersistence of microscopic foci

Surgical treatmentSurgical treatment

• Breast surgeryBreast surgery– Indications for surgical approach are Indications for surgical approach are

similar to patients who did not undergo similar to patients who did not undergo NASTNAST

– Definitive surgery should take place as Definitive surgery should take place as soon as the patient has recovered from soon as the patient has recovered from NAST toxicities (3-6 week window)NAST toxicities (3-6 week window)

– NAHT patients do not need to cease NAHT patients do not need to cease treatment prior to surgerytreatment prior to surgery

Surgical treatmentSurgical treatment

• Nodal evaluation following NAST:Nodal evaluation following NAST:– Clinically negative (cN0): outside of trial, sln Clinically negative (cN0): outside of trial, sln

bx may be done prior to or after NAST. If bx may be done prior to or after NAST. If neg, no further axillary evaluation is neg, no further axillary evaluation is required.required.

– Clinically positive (cN1/pN1): Clinically positive (cN1/pN1): • If remain clinically positive: ALNDIf remain clinically positive: ALND• If convert to clinically negative: If convert to clinically negative:

– ALNDALND– Posttherapy sln bx if dual tracer used, at least two Posttherapy sln bx if dual tracer used, at least two

nodes are recovered, and removal of prior biopsied nodes are recovered, and removal of prior biopsied node confirmed by image confirmation of clipnode confirmed by image confirmation of clip

SENTINA trial (2013)SENTINA trial (2013)

• cN0 baseline: pre-NACT sln bxcN0 baseline: pre-NACT sln bx– pN0: no further axillary evalpN0: no further axillary eval– pN1: post-NACT sln bx + ALNDpN1: post-NACT sln bx + ALND

• cN1 baseline: no pre-NACT bxcN1 baseline: no pre-NACT bx– cN0 post-NACT: sln bx + ALNDcN0 post-NACT: sln bx + ALND– cN1 post-NACT: ALND cN1 post-NACT: ALND

SENTINA trial (2013)SENTINA trial (2013)

• Results:Results:– In those who underwent a post-NACT sln bx In those who underwent a post-NACT sln bx

and ALND, patients who started out cN1 had and ALND, patients who started out cN1 had a higher sentinel node detection rate (80 vs a higher sentinel node detection rate (80 vs 61%) and a lower FN rate (14 vs 52%) 61%) and a lower FN rate (14 vs 52%) compared to those who started out pN1 compared to those who started out pN1 based on pre-NACT sln bx.based on pre-NACT sln bx.•Pre-NACT sln bx decreases success and accuracy Pre-NACT sln bx decreases success and accuracy

of post-NACT sln bx.of post-NACT sln bx.

•NACT may adversely impact success of sln bx.NACT may adversely impact success of sln bx.

ACOSOG Z1071 trial (2012)ACOSOG Z1071 trial (2012)

• Patients with cN1 disease at diagnosis Patients with cN1 disease at diagnosis underwent sln bx and ALND after NACT.underwent sln bx and ALND after NACT.

• Main results:Main results:– Sln detection rate was 93%Sln detection rate was 93%– 41% of cN1 patients converted to pN0 after NACT41% of cN1 patients converted to pN0 after NACT– FN rate in cN1 patients with at least 2 sln recovered FN rate in cN1 patients with at least 2 sln recovered

was 12.6% and dropped to 9.1% for 3 sln.was 12.6% and dropped to 9.1% for 3 sln.– FN rate lower with dual vs single agents (10.8 vs FN rate lower with dual vs single agents (10.8 vs

20.3%)20.3%)– Confirmed findings NSABP B-27 (dual agent) and B-Confirmed findings NSABP B-27 (dual agent) and B-

32 (FN rate decreases with more sln recovered)32 (FN rate decreases with more sln recovered)

Adjuvant therapyAdjuvant therapy

• Radiation therapy: XRT Radiation therapy: XRT recommendation typically based recommendation typically based upon pretherapy clinical stagingupon pretherapy clinical staging– BCT patientsBCT patients– LABC and IBC patients s/p mastectomyLABC and IBC patients s/p mastectomy– Patients with post-NAST residual nodal Patients with post-NAST residual nodal

diseasedisease

NSABP B-51 trialNSABP B-51 trial

– Randomized phase III clinical trial Randomized phase III clinical trial evaluating post-mastectomy chestwall evaluating post-mastectomy chestwall and regional nodal XRT and post-and regional nodal XRT and post-lumpectomy regional nodal XRT in lumpectomy regional nodal XRT in patients with positive axillary nodes patients with positive axillary nodes before NACT who convert pathologically before NACT who convert pathologically to pN0 after NACT.to pN0 after NACT.

Adjuvant therapyAdjuvant therapy

• Adjuvant chemotherapyAdjuvant chemotherapy– Typically not administer adjuvant chemo txTypically not administer adjuvant chemo tx– May consider adjuvant chemo tx if:May consider adjuvant chemo tx if:

•Residual TNBC is present and their NACT did not Residual TNBC is present and their NACT did not include both an anthracycline and a taxane.include both an anthracycline and a taxane.

•Patient treated with NAHT and is eligible for Patient treated with NAHT and is eligible for chemo tx.chemo tx.

•Patient did not complete planned NACT course.Patient did not complete planned NACT course.

Adjuvant therapyAdjuvant therapy

• Her 2 directed therapy:Her 2 directed therapy:– Resumption of trastuzumab to complete Resumption of trastuzumab to complete

full year coursefull year course– Initiation of trastuzumab if not part of Initiation of trastuzumab if not part of

their NAST regimentheir NAST regimen

• Endocrine therapy:Endocrine therapy:– Recommended in HR positive patients Recommended in HR positive patients

following locoregional treatmentfollowing locoregional treatment

Results Results

• CTNeoBC (2012)CTNeoBC (2012)– Patients with pCR had significant Patients with pCR had significant

improvement in EFS and OSimprovement in EFS and OS– The pCR rate varied by breast cancer subtypeThe pCR rate varied by breast cancer subtype

•HR +, Her 2 -, grade 1-2: 7%HR +, Her 2 -, grade 1-2: 7%•HR +, Her 2 -, grade 3: 16%HR +, Her 2 -, grade 3: 16%•HR +, Her 2 + (NACT + trastuzumab): 30%HR +, Her 2 + (NACT + trastuzumab): 30%•HR -, Her 2 -: 34 %HR -, Her 2 -: 34 %•HR -, Her 2 + (NACT + trastuzumab): 50%HR -, Her 2 + (NACT + trastuzumab): 50%

Working towards a central goal

The Stoddard Neoadjuvant The Stoddard Neoadjuvant Protocol Protocol

• Neoadjuvant therapy indicationsNeoadjuvant therapy indications– Absolute:Absolute:

• Inflammatory breast cancerInflammatory breast cancer

• Locally advanced T3/T4 tumors, particularly if Her 2 Locally advanced T3/T4 tumors, particularly if Her 2 positivepositive

– Relative:Relative:• Patients younger than 40 with tumors larger than 2 Patients younger than 40 with tumors larger than 2

cm regardless of nodal statuscm regardless of nodal status

• Her 2 + (T2 or N1) to allow use of pertuzumabHer 2 + (T2 or N1) to allow use of pertuzumab

• Stage II tumors not qualifying for de novo BCTStage II tumors not qualifying for de novo BCT

• N2/N3 disease, esp if hormone negativeN2/N3 disease, esp if hormone negative

The Stoddard Neoadjuvant The Stoddard Neoadjuvant ProtocolProtocol

• Prior to starting neoadjuvant Prior to starting neoadjuvant therapy:therapy:– Clinically suspicious breast and nodal Clinically suspicious breast and nodal

abnormalities should be biopsied and abnormalities should be biopsied and marked with radiopaque clips.marked with radiopaque clips.

– Clinical and pathological staging should Clinical and pathological staging should be completed prior to starting therapy.be completed prior to starting therapy.

The Stoddard Neoadjuvant The Stoddard Neoadjuvant ProtocolProtocol

• Imaging during NAST:Imaging during NAST:– Imaging at midpoint in therapy to assess Imaging at midpoint in therapy to assess

response. Exact timing will depend on regimen response. Exact timing will depend on regimen and treating physicians.and treating physicians.

– For women with baseline US clearly For women with baseline US clearly demonstrating the tumor prior to NAST and demonstrating the tumor prior to NAST and choosing mastectomy, repeat US utilized to choosing mastectomy, repeat US utilized to monitor response.monitor response.

– For women planning BCT after NAST, pre and For women planning BCT after NAST, pre and post-NAST MRI should be used to assess extent post-NAST MRI should be used to assess extent of resection.of resection.

Cases Cases

• 48yo, cT4d cN0 cM0, grade 3, IDC, +, -, +.48yo, cT4d cN0 cM0, grade 3, IDC, +, -, +.

• 60yo, cT3 cN1 cM0, grade 2, ILC, +, +, -.60yo, cT3 cN1 cM0, grade 2, ILC, +, +, -.

• 39yo, cT2 cN0 cM0, grade 2, IDC, -, -, +.39yo, cT2 cN0 cM0, grade 2, IDC, -, -, +.

• 37 yo, cT1c cN0 cM0, grade 3, IDC, -, -, -.37 yo, cT1c cN0 cM0, grade 3, IDC, -, -, -.

• 65 yo, cT2 cN0 cM0, grade 1, IDC, +, +, -.65 yo, cT2 cN0 cM0, grade 1, IDC, +, +, -.

• Who would you offer NAST to?Who would you offer NAST to?

Summary Summary

• All patients who are candidates for systemic All patients who are candidates for systemic therapy are candidates for NASTtherapy are candidates for NAST

• If the indication for systemic therapy is If the indication for systemic therapy is uncertain, then surgical therapy should be uncertain, then surgical therapy should be completed firstcompleted first

• NAST should be tailored to the biologic profile NAST should be tailored to the biologic profile of the tumorof the tumor

• Primary tumor and nodes must be measurable Primary tumor and nodes must be measurable and monitoredand monitored

• A multidisciplinary team approach must be A multidisciplinary team approach must be availableavailable