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

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

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

Why not? Patient anxiety Cost

Who to stage for metastatic disease? What staging investigations?

Baseline staging tests after a new diagnosis of breast cancer: further evidence of their limited indications. Puglisi F et al 2005. Annals of Oncology 2005;16:263-266. 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

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%)

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

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

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%)

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

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

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

Ravaioli A et al. Breast Cancer Res Treat 2002;72(1):53-60. Diagnoses of metastatic disease Bone scan: 37 / 1193 (3.1%) CXR: 8 / 1206 (0.7%) Liver ultrasound: 10 / 1206 (0.8%)

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 N0-1  1.46% metastases detection (2) pT1-3 N2, pT4  10.68% metastases detection

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):1439-1444. 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])

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)

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

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

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)

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

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  

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