This document discusses the case of a 48-year-old female diagnosed with grade III invasive ductal carcinoma of the right breast in 2014. She received breast-conserving surgery along with sentinel lymph node biopsy, which showed triple positive disease. She was treated with FEC chemotherapy but received no further adjuvant treatment. In 2018, she presented with local recurrence and underwent a right modified radical mastectomy. The document discusses treatment options and ongoing clinical trials for triple positive breast cancer. Panelists debate preferences for first-line and second-line treatment of metastatic triple positive disease.

1. DR. R. RAJKUMAR D.M.
CONSULTANT MEDICAL ONCOLOGIST
MADURAI MEDICAL COLLEGE &
VELAMMAL SPECIALITY HOSPITALS
PANEL DISCUSSION

2. CASE DISCUSSION
▪ 48YRS OLD FEMALE THANJAVUR
▪ CA Rt BREAST ( OCT 2014)
▪ BCS (Rt) –WLE+SENTINEL LYMPHNODE
BIOPSY
▪ HPE- IDC GRADE III

3. CASE DISCUSSION

4. CASE DISCUSSION
▪ RECEIVED 3× FEC ( JAN 2015)
▪ NO FURTHERTREATMENT

5. CASE DISCUSSION
▪ RECEIVED 3× FEC ( JAN 2015)
▪ NO FURTHERTREATMENT
▪ LOCAL RECURRENCE (3/2018)
▪ Rt MRM TRICHY

6. CASE DISCUSSION

7. CASE DISCUSSION

8. CASE DISCUSSION
▪ 48YRS OLD FEMALE THANJAVUR
▪ CA Rt BREAST ( OCT 2014)
▪ BCS (Rt) –WLE+SENTINEL LYMPHNODE
BIOPSY
▪ HPE- IDC GRADE III

9. QUESTION - SURGICAL ONCOLOGIST
BCS+SLNB+FS
1.AGREE
2.DONT AGREE
3.MAY BE
4.DONT KNOW

10. CASE DISCUSSION

11. ▪TRIPLE POSITIVE
1. BELIEVE
2. DONT BELIEVE
3. MAY BE
4. DONT KNOW
CASE DISCUSSION PATHOLOGIST

12. CASE DISCUSSION
▪ RECEIVED 3× FEC ( JAN 2015)
▪ NO FURTHERTREATMENT
▪ LOCAL RECURRENCE (3/2018)
▪ Rt MRM TRICHY

13. QUESTION - RADIATION ONCOLOGIST
▪WBI /PBI AFTER BCS
1. REQUIRED
2. NOT REQUIRED
3. MAY BE
4. DONT KNOW

14. QUESTION MED ONCOLOGIST
WHAT IS UR PREFERRED CHOICE OFTREATMENT FOR
TRIPLE POSITIVE MBC ?
1. CHEMO + HERCEPTIN
2. ENDO + HERCEPTIN
3. CHEMO + ENDO + HERCEPTIN
4. ENDO + HERCEPTIN + CD 4/6 INHIBITORS

15. CASE DISCUSSION

16. CASE DISCUSSION

17. CASE DISCUSSION

18. CASE DISCUSSION

19. QUESTION MED ONCOLOGIST
WHAT IS UR PREFERRED CHOICE OFTREATMENT FOR
TRIPLE POSITIVE MBC - II LINE ?
1. CHEMO + HERCEPTIN
2. ENDO + HERCEPTIN
3. CHEMO + ENDO + HERCEPTIN
4. ENDO + HERCEPTIN + CDK 4/6 INHIBITORS
5. ENDO+ LAPATINIB + CDK 4/6 INHIBITORS

20. TPBC

21. CASE DISCUSSION
▪ University of Colorado Denver clinical database, among 114 HR+/HER2+ cases,
▪ 71% were triple positive, 21% were ER+/PR-/HER2+, and 8% were ER-/PR+/HER2+
▪ 40-50% of these tumors belong to HER2-enriched PAM50 molecular subtype, while the rest
are classified as luminal A or B subtype

22. CASE DISCUSSION

23. Cleopatra

24. TDM-1: EMILIA
Verma S ESMO 2012
(Activity HR+/HR-)

25. Disease involvement
Visceral
Nonvisceral
452
150
150
48
95
34
3.4
3.1
302
102
168
51
6.2
6.7
0.56
0.41
(0.44, 0.72)
(0.26, 0.64)
≤3
4–5
Number of prior regimens
for advanced BC
>5
209
214
177
78
65
55
49
45
35
3.3
3.7
2.9
131
149
122
60
83
75
6.9
6.2
5.8
0.48
0.58
0.48
(0.32, 0.70)
(0.40, 0.83)
(0.32, 0.73)
TDM-1:TH3RESA Study (PFS Subgroup Analyses)
TPC
ER and PR status
ER+ and/or PR+
ER– and PR–
Unknown
311
270
21
103
85
10
66
58
5
3.9
2.9
3.9
208
185
11
109
105
5
5.9
6.0
8.3
0.56
0.51
0.17
(0.41, 0.76)
(0.37, 0.71)
(0.03, 0.93)
T-DM1
Better
TPC
Better
Baseline
characteristic
Total
n n Event
Median
(months) n Event
Median
(months)
All patients 602 198 129 3.3 404 219 6.2 0.52 (0.42, 0.65)
a Unstratified HR.
By Investigator Assessment
Brain metastasis at baseline
Yes
No
67
535
27
171
16
113
2.9
3.6
40
364
24
195
5.8
6.2
0.47
0.53
(0.24, 0.89)
(0.42, 0.66)
T-DM1
0.2 0.5 1 2 5
HRa (95% CI)
Krop I et al Lancet Oncol 2014

26. Small but signif. advantage
Eve: less efficacy in HR+(Her2+)
Her2+

27. Her2+
No
differences
Eve: benefit in HR- (Her2+)

28. At least two types of genetic HER2+ tumours
The Cancer Genome Atlas Network, Nature 2012

29. CASE DISCUSSION

30. Prat et al JNCI 2014
Her-2 heterogeneity
IHC
Cancer Genome Atlas + Metabric datasets
Subtype is more
informative than
HER2-status on
breast cancer specific
DFS

32. Cross talk and resistance to endocrine therapy
HER1/HER2
Alteration ER
Tamoxifen
Ais
Fulvestrant?
Direct ER phosphorilation
Recruitment of co-activators
Repression or ER functions
Repression of ER synthesis
Tumor cell proliferation

33. Crosstalk to explain resistance to HER2-inhibitors
HER2
Alteration
ER
Trastuzumab
Lapatinib
Pertuzumab
- Repression of HER2 synthesis
- Escape through ER
Tumor cell proliferation

34. ER-HER2 crosstalks
Miller T W et al. JCO 2011;29:4452-4461

35. ER and HER2 simultaneous targeting
HER2
Alteration
ER
Trastuzumab
Lapatinib
Pertuzumab
Tamoxifen
Ais
Fulvestrant?
Tumor Cell Death

36. CROSS TALK

37. CROSS TALK

38. ONGOING TRIALS IN TPBC

39. CASE DISCUSSION

40. CASE DISCUSSION

41. CASE DISCUSSION

42. CASE DISCUSSION

43. CASE DISCUSSION

44. CASE DISCUSSION

45. COST

46. CASE DISCUSSION

47. CASE DISCUSSION

48. QUESTION MED ONCOLOGIST
WHAT IS UR PREFERRED CHOICE OFTREATMENT FOR
TRIPLE POSITIVE MBC - II LINE ?
1. CHEMO + HERCEPTIN
2. ENDO + HERCEPTIN
3. CHEMO + ENDO + HERCEPTIN
4. ENDO + HERCEPTIN + CDK 4/6 INHIBITORS
5. ENDO+ LAPATINIB + CDK 4/6 INHIBITORS

49. CASE DISCUSSION