1. Dr T P E Wells 13 July 2018 Breast SSG Bath
Patients with early breast cancer and asymptomatic for metastatic disease: do they need staging investigations?
Dr T P E Wells
13 July 2018
Breast SSG
Bath

2. Staging in early breast cancer asymptomatic for metastatic disease
Why and why not? Who to stage for metastatic disease? What staging investigations? Recommendations for practice

3. Why? To identify patients with incurable disease so that:
a more realistic prognosis can be given
treatment can be tailored accordingly

4. Why not?
Patient anxiety
Cost

5. Who to stage for metastatic disease? What staging investigations?

6. Baseline staging tests after a new diagnosis of breast cancer: further evidence of their limited indications. Puglisi F et al Annals of Oncology 2005;16:
University Hospital of Udine, Italy
516 consecutive patients with newly diagnosed invasive breast cancer
Referred from February 1999 to August 2003
Patients with clinical signs of potential metastases were excluded
At baseline: 412 bone scans, 412 liver ultrasounds, 428 CXR

7. Puglisi F et al 2005. Annals of Oncology 2005;16:263-266.
Pre-imaging stage
Bone scan (%)
Liver ultrasound (%)
CXR (%)
All stages (I – III)
26 / 412 (6.31%)
3 / 412 (0.72%)
4 / 428 (0.93%) I
12 / 236 (5.08%)
0 / 232
0 / 234 II
7 / 126 (5.55%)
0 / 127
0 / 139
III
7 / 50 (14%)
3 / 53 (5.66%)
4 / 55 (7.27%)

8. Puglisi F et al 2005. Annals of Oncology 2005;16:263-266.
Conclusion
stage I and II breast cancer should not be routinely scanned with liver ultrasound and CXR at baseline
questionable whether bone scan should be performed in stage I and II disease
recommend baseline staging tests for stage III breast cancer

9. Baseline staging of newly diagnosed breast cancer – Kuwait Cancer Control Centre experience. Abuzallouf et al. Med Princ Pract 2007;16:22-24.
Retrospective review of patients’ files with newly diagnosed breast cancer treated with surgery and subsequent therapy
Kuwait Cancer Control Centre
1993 to 1998
823 consecutive patients, asymptomatic for metastatic disease
38 excluded because of inadequate information

10. Abuzallouf et al. Med Princ Pract 2007;16:22-24.
Staging: physical examination, bone scan, CXR, liver ultrasound
Metastases found in 36 / 785 patients (4.6%):
Bone: 29 / 785 (3.7%)
Lung: 6 / 785 (0.8%)
Liver: 5 / 785 (0.6%)

11. Abuzallouf et al. Med Princ Pract 2007;16:22-24.
Metastases in 0.7% (stage I and II) and 16.2% (stage III), p=0.0001
Bone metastases
3/587 (0.5%) stage I and II
26/198 (13.1%) in stage III
Lung metastases
0/587 (0%) stage I and II
6/198 (3%) in stage III
Liver metastases
1/587 (0.5%) stage I and II
4/198 (2%) in stage III

12. Abuzallouf et al. Med Princ Pract 2007;16:22-24.
Conclusion
low yield of metastases in asymptomatic patients with stage I and II breast cancer
incidence of metastases in locally advanced disease is higher and staging investigations are warranted

13. Staging of breast cancer: new recommended standard procedure
Staging of breast cancer: new recommended standard procedure. Ravaioli A et al. Breast Cancer Res Treat 2002;72(1):53-60.
Retrospective study
Oncology Departments of Rimini and Forli, Italy
Data from 1218 consecutive cases of breast cancer
Referred between November 1998 and March 2000
Pathological and biological parameters, investigations performed at diagnosis and during 6 months of follow up
Median age 68 years (range 24 – 89)
836 (68.6%) postmenopausal, 382 (31.4%) premenopausal

14. Ravaioli A et al. Breast Cancer Res Treat 2002;72(1):53-60.
Diagnoses of metastatic disease
Bone scan: / 1193 (3.1%)
CXR: / 1206 (0.7%)
Liver ultrasound: 10 / 1206 (0.8%)

15. Ravaioli A et al. Breast Cancer Res Treat 2002;72(1):53-60.
Logistic regression for observing distant metastases:
significant odds ratios for pT status and nodal status
odds ratio 3.09 (95% CI 1.09 – 8.75, p=0.03) for pT4 vs. pT1
odds ratio 5.03 (95% CI 1.72 – 14.62, p<0.001) for 4-6 nodes vs. pN0
odds ratio 6.71 (95% CI 3.48 – 18.14, p<0.001) for > 6 nodes vs. pN0
No significant difference for observing distant metastasis for subsets according to histological grading (p=0.12)and receptor status (p=0.77)
Findings suggest that can divide breast cancer into two subgroups
(1) pT1-3 N  1.46% metastases detection
(2) pT1-3 N2, pT  10.68% metastases detection

16. Systematic review of the evidence and indications for:
Baseline staging tests in primary breast cancer: a practice guideline. Myers R E et al. CMAJ 2001;164(10):
Breast Cancer Disease Site Group of the Cancer Care Ontario Practice Guidelines Initiative
Systematic review of the evidence and indications for:
routine bone scans, liver ultrasonography, CXR in asymptomatic women who have undergone surgery for breast cancer
Database search of:
MEDLINE and CANCERLIT (articles published from 1966 to July 1998)
Cochrane library (1999 [Issues 1 and 4] and 2000 [Issue 1])

17. Myers R E et al. CMAJ 2001;164(10):1439-1444.
11 studies of bone scanning (1972 to 1980), 1307 women:
bone metastases in 6.8% (stage I), 8.5% (stage II), 24.5% (stage III)
9 studies of bone scanning (1985 to 1995), 5407 women:
bone metastases in 0.5% (stage I), 2.4% (stage II), 8.3% (stage III)
4 studies of liver ultrasonography (1988 to 1993), 1625 women:
Liver metastases in 0% (stage I), 0.4% (stage II), 2.0% (stage III)
2 studies of CXR (1988 to 1991), 3884 patients:
Lung metastases in 0.1% (stage I), 0.2% (stage II), 1.7% (stage III)

18. Myers R E et al. CMAJ 2001;164(10):1439-1444.
False positive rates:
10% to 22% for bone scanning
33% to 66% for liver ultrasonography
0% to 23% for CXR
False negative rates:
10% for bone scanning

19. Myers R E et al. CMAJ 2001;164(10):1439-1444.
When determining recommendations, Group members felt that tests that detected metastases in less than 1% of patients and had a significant false positive rate were not clinically useful
Recommendations
no post-operative staging needed for stage I breast cancer
bone scan for stage II breast cancer
bone scan, liver ultrasound and CXR for stage III breast cancer

20. To discuss – who to stage?
Stage I and stage II disease:
postoperative staging not recommended
? bone scan for stage II disease
Stage III disease
tumour > 5 cm and mobile involved axillary nodes
any size tumour and ≥ 4 involved axillary nodes
fixed involved axillary nodes
tumour involving surrounding tissue (T4 disease)

21. Breast cancer staging AJCC staging version 5 Stage I T1 N0 M0
Stage IIA T1 N1 M0, T2 N0 M0
Stage IIB T2 N1 M0, T3 N0 M0
Stage IIIA T1-2 N2 M0, T3 N1-2 M0
Stage IIIB T4 any N M0, any T N3 M0
Stage IV any T any N M1

22. Breast cancer staging AJCC staging version 5
Stage I tumour ≤ 2cm and uninvolved axillary nodes
Stage II tumour > 2 cm and uninvolved axillary nodes
mobile involved axillary nodes and tumour ≤ 5 cm
Stage III mobile involved axillary nodes and tumour > 5 cm
fixed involved axillary nodes and any size tumour
tumour involving surrounding tissue
ipsilateral internal mammary node involvement
Stage IV distant spread

23. To discuss – what staging investigations?
bone scan
bone scan, liver ultrasound, CXR
bone scan, CT chest abdomen pelvis
CT chest abdomen pelvis
PET-CT