Understanding the new breast cancer staging system and the prognostic impact on survival

1. Breast Cancer Staging 2018
www.aboutcancer.com www.aboutcancer.com

2. What tests do you need to stage
someone with breast cancer?

3. www.nccn.org

4. Tests need to properly stage a woman with breast cancer
Most cases: just mammogram (and possibly ultrasound) and routine blood work and
careful review of the biopsy (pathology review)
Optional:
Breast MRI may be useful to the surgeon if the woman has dense breasts and a
lumpectomy is being considered
Other scans (like CT scan or bone or liver or brain scan) only if symptoms or abnormal
blood tests
PET scan generally reserved for high risk cases (e.g. multiple lymph node spread or
triple negative cancers)

5. www.cap.org for CAP Cancer Protocols
Note that this is 32 pages long!

6. Now includes not just TNM (tumor, nodes, metastases) but also biomarkers (estrogen
receptor ER, grade and HER2) and even genomics (OncotypeDx)

7. Now includes not just TNM (tumor, nodes, metastases) but also biomarkers (estrogen
receptor ER, progesterone PR, grade and HER2) and even genomics (OncotypeDX)

8. Start with the Tumor Size or T Stage
T1 up to 2 cm and T2 >2cm up to 5cm and T3 > 5cm

9. Tumor Invasion for T4 Stage
T4a chest wall T4b skin nodules T4b edema T4c skin and chest
T4d Inflammatory: diffuse erythema and edema > 1/3 breast)

10. Then Look at Lymph
Nodes for N Stage
3 Levels of Axillary
Nodes
Supraclavicular
Nodes
Internal Mammary
Nodes

11. Clinical Lymph Node Stages (i.e. before surgery)

12. Pathologic Node Status Based on Size of Cancer in the Node
N0 (i+) isolated tumor cells no large than 0.2mm , if larger and up to 2mm called
N1mi for microscopic, if > 2mm then macro node or N1

13. Pathologic Node Status Based Number of Nodes

14. Pathologic Node Status Based Location of Nodes

15. Pathologic Node Status
Based on Location and
Number of Nodes

16. Genomic Classes Not in Use Yet
Genomics = the genes (and mutations) found
in the cancer biopsy

17. Luminal A – high estrogen receptor positive , negative
on HER2 , and low grade or low Ki-67 , best outlook
Basal Like – triple negative (negative for estrogen,
progesterone and HER2) and they have the worst
outlook
Genomic Classes

18. Distant Metastatic Free Survival by Genomic Groups
Luminal A best
Basal Worst

19. Local and regional recurrence by
patient group
Triple Negative worst
Luminal A - second best

20. Local and regional recurrence by
patient group
HER2 second worst
HER2 is best if you treat with
Herceptin

21. Things That Affect Prognosis (DSS = disease specific survival at 5 Years)

22. Outcome if Combine TNM Stage with other High Risk Biomarkers
Add one point for each of
these additional risk factors
DSS = disease specific survival
(do not die from breast
cancer)
OS = overall survival

23. 5 Year Disease Specific Survival by Stage and Risk Points
0 points
1 point
2 points
3 points
Stage based on TNM

24. Pathologic Prognostic Stage

29. Exceptions to the Rule
Any distant metastases is always Stage IV
Low risk Oncotype keeps the early stages as IA

30. 10 Year Risk of Distant Relapse after Tamoxifen (5y)
In Node Negative Patients
Recurrence Score
RiskofRelapse
Genomics:
Test the gene
mutations in the
cancer biopsy ,
should predict
how dangerous
the cancer is, or
the risk of a
relapse or
recurrence

31. 10 Year Risk of Distant Relapse after Tamoxifen (5y)
In Node Negative Patients
Recurrence Score
RiskofRelapse
Genomic testing on the
cancer will determine the
recurrence score

32. 10 Year Risk of Distant Relapse after Tamoxifen (5y)
In Node Negative Patients
Recurrence Score
RiskofRelapse
A low risk recurrence score
predicts the risk of relapse
treated with Tamoxifen
Recurrence score of 8
Risk of a relapse
only 7%

33. 10 Year Risk of Distant Relapse after Tamoxifen (5y)
In Node Negative Patients
Recurrence Score
RiskofRelapse
A high risk recurrence
score predicts the risk of
relapse treated with
Tamoxifen Recurrence score of 44
Risk of a relapse 31%
so needs to consider
adding
chemotherapy to
the hormone
therapy

34. Endocrine Therapy or Chemotherapy for Node Negative, ERP+, HER2 - , Based on
Recurrence Score (TAILORx Trial) NEJM 2018
Freedom from Recurrence/9y 1- 10 11-25 26+
Endocrine 99% 92%
Chemo/Endo 93% 85%
Overall Survival/ 9y
Endocrine 94% 94%
Chemo/Endo 94% 89%
Recurrence Score
Score 1-10 (Low Risk) 11-25 (Intermediate) 26+ (High Risk)

35. Endocrine Therapy or Chemotherapy for Node Negative, ERP+, HER2 - , Based on
Recurrence Score (TAILORx Trial) NEJM 2018
Freedom from Recurrence/9y 1- 10 11-25 26+
Endocrine 99% 92%
Chemo/Endo 93% 85%
Overall Survival/ 9y
Endocrine 94% 94%
Chemo/Endo 94% 89%
Recurrence Score
Score 1-10 (Low Risk)
Low Risk, Node Negative patients do quite well with only hormone
therapy and chemotherapy not necessary

36. Endocrine Therapy or Chemotherapy for Node Negative, ERP+, HER2 - , Based on
Recurrence Score (TAILORx Trial) NEJM 2018
Freedom from Recurrence/9y 1- 10 11-25 26+
Endocrine 99% 92%
Chemo/Endo 93% 85%
Overall Survival/ 9y
Endocrine 94% 94%
Chemo/Endo 94% 89%
Recurrence Score
11-25 (Intermediate) 26+ (High Risk)
Intermediate Risk, Node Negative patients do quite well with only hormone
therapy and gain very little with the addition of chemotherapy (unless
younger than 50)

37. Recurrence or Mortality with 1 – 3 Nodes +
Tamoxifen
ChemoRx +
Tamoxifen
Rate
Lets you compare the results with hormone
therapy alone or combined with chemotherapy
Genomics
testing in node
positive cases
to see if
chemotherapy
is better than
hormone
therapy in all
cases

38. Recurrence or Mortality with 1 – 3 Nodes +
Tamoxifen
ChemoRx +
Tamoxifen
RelapseRate
Low Score
Low recurrence score
Recurrence Score

39. Recurrence or Mortality with 1 – 3 Nodes +
Tamoxifen
ChemoRx +
Tamoxifen
RelapseRate
Low Score
ChemoRx
Tamoxifen
Low recurrence score, the
relapse rate is lowest with
Tamoxifen alone
(chemotherapy of no benefit)
Recurrence Score

40. Recurrence or Mortality with 1 – 3 Nodes +
Tamoxifen
ChemoRx +
Tamoxifen
High Score
High recurrence score
Recurrence Score

41. Recurrence or Mortality with 1 – 3 Nodes +
Tamoxifen
ChemoRx +
Tamoxifen
High Score
Tamoxifen worse
ChemoRx
best
High recurrence score Chemo Best
Recurrence Score

42. Recurrence or Mortality with 4 + Nodes +
Low Intermed High
Tamoxifen
Tamoxifen +
ChemoRx
At some point the benefits of
chemotherapy become obvious

43. Which is more important, the clinical risk categories or the
genomic analysis. What if they give conflicting information?
Does Mammaprint Outweigh the Clinical Risk in deciding on
ChemoRx (MINDACT Trial, NEJM Aug 25, 2016)

44. Clinical Stage = High Risk (should benefit from Chemotherapy)
Genomics = Low Risk (no need for chemotherapy)
Cure Rate (DMFS)
Nodes Involved No Chemo Yes Chemo
None 93.2% 95.7%
Yes 95.6% 96.3%
DMFS = distant metastatic free survival
Conclusion: genomics trumps clinical stage in avoiding chemotherapy

45. Clinical Stage = Low Risk (would not from Chemotherapy)
Genomics = High Risk (may need chemotherapy)
Cure Rate (DMFS)
Nodes Involved No Chemo Yes Chemo
None 95.1% 96%
DMFS = distant metastatic free survival
Conclusion: genomics does not trump clinical stage in adding
chemotherapy

46. Combing the risk factors to determine the outcome by different therapies,
The use of online calculators or genomics
Adjuvant Online (currently unavailable)
Predict: www. predict.nhs.uk
CancerMath.net

47. 0
10
20
30
40
50
60
70
80
0 4 8 12 16 20
Number of Positive Nodes
15 Year Overall Survival Based on Tumor Size and
Number of Lymph Node Metastases
Calculation
based on 66 yo
woman with
ERP+ and HER2-,
2.5cm , grade 2
invasive ductal
cancer using
PREDICT and
treated with
Chemo +
Hormone Rx
1 cm
2.5 cm
4 cm
8 cm
predict.nhs.uk

48. 15 Year Overall Survival Based on Tumor Size and
Number of Lymph Node Metastases
The size is
less
important
if the
number of
nodes
involved is
small

49. 15 Year Overall Survival Based on Tumor Size and
Number of Lymph Node Metastases
Note the higher the number of involved nodes, the worse the survival
The bigger the
tumor, the
worse the
impact of the
nodes

50. 0
10
20
30
40
50
60
70
80
0 4 8 12 16 20
percent
Positive Lymph Nodes
Surgery
Surgery +
Hormone Rx
S + H +
Chemotherapy
15 Year Overall Survival Based on Therapy and Number
of Lymph Node Metastases
Calculation
based on 66 yo
woman with
ERP+ and HER2-,
2.5cm , grade 2
invasive ductal
cancer using
PREDICT
predict.nhs.uk

51. In high risk
women with a
large number
of nodes, the
benefits of
chemotherapy
is large
In low risk
women with a
small number
of nodes, the
benefits of
chemotherapy
are small
15 Year Overall Survival

52. http://cancer.lifemath.net
/index.html
Other calculators to
determine the benefit
from more intensive
therapy

53. www.aboutcancer.com www.aboutcancer.com
aboutcancer.com/videos youtube.com/user/robertmillermd/videos