early breast cancer: (neo-) adjuvant endocrine therapy...luminal early breast cancer: endocrine...

CAMPUS GROSSHADERN

CAMPUS INNENSTADT

KLINIK UND POLIKLINIK FÜR FRAUENHEILKUNDE UND GEBURTSHILFE

DIREKTOR: PROF. DR. MED. SVEN MAHNER

Brustzentrum der

Universität

München

Leitung:

Prof. Nadia Harbeck

Luminal early breast cancer: (neo-) adjuvant endocrine therapy

Nadia HarbeckBreast Center, University of Munich, Germany

Brustzentrum

Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe

KLINIKUM DER UNIVERSITÄT MÜNCHEN®

Luminal EBC: (Neo-)adjuvant endocrine therapy

▪ Treatment concepts

▪ Pre- and postmenopausal patients

▪ Choice of agents

▪ Duration

▪ Open questions:

▪ Neoadjuvant endocrine therapy

▪ Adherence

▪ YOUR Questions

11.11.20172

Luminal early breast cancer | Prof. Harbeck

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Therapy strategies in early breast cancer

11.11.20173 Harbeck & Gnant, Lancet 2017


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11.11.20174


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LOW ER EXPRESSION ISCORRELATED WITH NON-LUMINALCHARACTERISTICS

11.11.20175 Iwamoto et al, JCO 2011


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LOW ER EXPRESSION AND OUTCOME IN EARLY BREAST CANCER

11.11.20176 Iwamoto et al, JCO 2011


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Breast

cancer

Breast

cancer

Ovary

NNR

Modified after Tellez C, et al. Surg Oncol Clin North Am. 1995;4:751-777.

GnRH = Gonadotropin-Releasing Hormone

LH = Luteinising hormone

FSH = Follicle-stimulating hormone

Postmenopausal

PostmenopausalPremenopausal

LHFSH

GnRH Analogon

Antiestrogenes

Antiestrogenes

Estrogenes Estrogenes

Androgenes

Aromataseinhibitors

Peripheral Aromatization

Endocrine therapy for breast cancer

11.11.20177


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EBCTCG METAANALYSIS: TAMOXIFEN AND AGE AT STUDY ENTRY

11.11.20178 ECBCTG, Lancet 2011


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EBCTCG METAANALYSIS: TAMOXIFEN AND ER/PR EXPRESSION

11.11.20179 ECBCTG, Lancet 2011


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EBCTCG METAANALYSIS: TAMOXIFEN AND ER/PR STATUS

11.11.201710 ECBCTG, Lancet 2011


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EBCTCG METAANALYSIS: TAMOXIFEN AND CHEMOTHERAPY

11.11.201711 ECBCTG, Lancet 2011


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▪ Premenopausal patients

11.11.201712


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11.11.201713 Lancet 2007

ROLE OF OVARIAN SUPPRESSION


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11.11.201714

Francis et al, SABCS 2014


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11.11.201715

Francis et al, SABCS 2014


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JOINT ANALYSIS OF TEXT AND SOFT

11.11.201716 Pagani et al, ASCO 2014


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Ovarian suppression: How about tolerability?

11.11.201717


Francis et al, SABCS 2014;

Ribi et al, SABCS 2014

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Local

Treatment

Goserelin

3 Years

Tam 3 years

Tam 3 years

+ Zol

Ana 3 years

+ Zol

Ana 3 years

Gnant M et al. Lancet Oncol 2011

ABCSG 12 Trial: OS worse with Anastrozole versus Tamoxifen

HR 1,75 ; CI 1,08-2,83; p=0,02

▪ Premenopausal pts

(n=1803)

▪ ER a/o PR pos

▪ Stage 1 and 2

▪ CHT only preop (in 5%)

▪ Primary endpoint: DFS

11.11.201718


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Having amenorrhea is not the same as beingpostmenopausal !

11.11.201719 Smith et al, JCO 2016


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▪ Prostmenopausal patients

11.11.201720


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EBCTCG METAANALYSIS: TAMOXIFEN VS. AI (N=31,920 POSTMENOPAUSAL PATIENTS)

11.11.201721 ECBCTG, Lancet 2015


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EBCTCG METAANALYSIS: TAMOXIFEN VS. AI (POSTMENOPAUSAL)

11.11.201722

ECBCTG, Lancet 2015


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EBCTCG METAANALYSIS: TAMOXIFEN UPFRONT VERSUS SEQUENTIAL TAMOXIFEN → AI (POSTMENOPAUSAL)

11.11.201723

ECBCTG, Lancet 2015


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BIG 1-98: Breast Cancer Events (TAM → LET vs. LET)

11.11.201724

According to Nodal Status*

0 1 2 3 4 5 6

0

5

10

15

20

Bre

ast

can

cer

recu

rren

ce,

%

Time from randomization, years

7.9

4.7

1.3

0.9

14.7

12.4

4.9

3.5

Node-positive

Node-negative

Total Population20

4.1

9.1

7.3

2.5

0 1 2 3 4 5 6

0

5

10

15

Bre

ast

can

cer

recu

rren

ce,

%

Time from randomization, years

TAM LETLetrozole

Mouridsen H et al. NEJM 2009;361:766–76.TAM, Tamoxifen; LET, Letrozol

TAM LETLetrozole

*42% of the population are node positive; 58% are node negative


© AGO e. V.in der DGGG e.V.

sowie

in der DKG e.V.

Guidelines Breast

Version 2012.1D

www.ago-online.de

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PRE- AND POSTMENOPAUSAL PATIENTS: ALGORITHM

11.11.201726 Papakonstantinou et al, JCO 2016


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Luminal EBC: Endocrine therapy

▪ How long is long enough ?

11.11.201727


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EBCTCG METAANALYSIS: DURATION OF TAMOXIFEN

11.11.201729

EBCTCG


10 vs 5 years of tamoxifen: Recurrence reduction by nodal status

NNT node positive = 20NNT node negative = 33

Endometrial cancers

Continue (3470)

Stop(3486)

P value

Endometrial cancers

102 47 <0.0001

Endometrial cancer deaths

31 23 0.27

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11.11.201734

San Antonio 2016 | Prof. Harbeck

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MA.17R: Disease-Free Survival (Median FU 6.3 yrs)

Letrozole

Placebo

5-year DFS:

95% LET vs. 91% PLAC Presented by: P.E. Goss, ASCO 2016

HR DFS: 0.66

p = 0.01

Let Plac

Subjects who had a DFS event

67 (7.0%) 98 (10.2%)

Distant recurrence 42 (4.4%) 53 (5.5%)Loco-regional recurrence

19 30

Bone 28 37Contralateral breast cancer§ CBC

13 (1.4%) 31 (3.2%)

5-year DFS:

95% LET vs. 91% PLAC

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TRANSATAC: Identification of late relapses

11.11.201738 Sestak et al, SABCS 2016


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EDUCATIONAL MATERIALS DO NOT IMPROVE COMPLIANCE

11.11.201740


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CANKADO: a digital patient diary

11.11.201741

✓ Drug intake (adherence)✓ Per intake, daily

✓ Symptoms and Management of adverse effects

✓ (based on CTCAE 4.0)✓ Daily

✓ Pain scale✓ Daily

✓ Quality of Life (QoL)✓ Daily, weekly or other intervals possible

✓ Dynamic Questionnaires ✓ Daily, weekly or other intervals possible

www.cankado.com

„Best of (freie Vorträge)“


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Luminal EBC

▪ Neoadjuvant endocrine therapy

11.11.201742


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11.11.201743


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Luminal EBC: Small neoadjuvant trials (n~800) with

early response assessment predict outcome of large phase III trials (n~11,000)

11.11.201744


Dowsett et al, 2005; Howell et al,2007; Kuter et al, 2012; DiLeo et al, 2014; Ellis et al, 2011 & 2017; Smith et al, 2017

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11.11.201745


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Luminal early breast cancer: Endocrine therapy

✓ ET is the adjuvant standard therapy with a standard duration of 5 years – it reduces the relative risk of relapse by ~25%.

✓ Extended adjuvant therapy 5-10 (15) years is effective, in particular in high-risk patients. Benefit and side effects need to be discussed with patients.

✓ For premenopausal patients, tamoxifen is standard; addition of GnRH analoga or AI plus GnRH are options for high-risk young patients

✓ For postmenopausal patients, Aromatase inhibitors (AI) or Tamoxifen are evidence-based options (upfront / sequential): Preference for AI upfront in high-risk and lobular tumors.

✓ Adherence is key for benefit – eHealth (www.cankado.com) approaches may be helpful for therapy support and enhanced physician-patient communication

11.11.201746



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11.11.201747

www.karger.com/brc

EVIDENCE-BASED, PATIENT-ORIENTED BREAST CANCER THERAPY

AGO (DKG, DGGG) www.ago-online.de

Annually revised, evidence-based

recommendations for diagnosis and treatment

www.cankado.comThe Digital Diary for Every Patient

early breast cancer: (neo-) adjuvant endocrine therapy...luminal early breast cancer: endocrine...

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