Silvia Michieletto

Staging of locally advanced breast cancer and the prediction of response to neoadjuvant chemotherapy: complementary role of scintimammography and 18F-FDG PET/CT.

BACKGROUND The primary endpoint of the study was to established the role of sestamibi scintimammography and PET/CT findings in locally advanced breast cancer (LABC) before neoadjuvant systemic therapy (NST) in different histological subtypes. The secondary endpoint was to determine the role of FDG PET/CT as multi-drug resistance marker. METHODS From January 2012, we prospectively enrolled 51 consecutive women (median age: 49 years; range: 27-76 yrs) with a biopsy-proven LABC. All patients underwent both sestamibi scintimammography and FDG PET/CT within one week before to start NST. Both examinations were qualitatively and semiquantitatively analysed. For scintimammography we calculated the tumor to background ratio (T/B) and the most intense uptake of the tumor to background ratio (I/B) according the following formula: T/B=[cntsT-cntsB]/ [cntsB] and I/B [cntsI-cntsB]/[cntsB]. Furthermore, the percentage washout index (WO) for T and I were obtained, according to: WOT,I= [cntsT,I]early image-[cntsT,I]delayed image/[cntsT,I]early image. Maximum and average (avg) standardized uptake value (SUV) was computed by PET/CT, using a region of interest. Patients who had an evidence of systemic metastases or a second active cancer at imaging scans, were excluded. At the end of pre-operative therapy, the response to therapy was assessed by the analysis of surgical specimen and then correlated with both scintimammographic and PET/CT data. RESULTS Based on the inclusion criteria, the final analysis was performed in 49 patients. Scintimammography and PET/CT showed a sensitivity of 100% for the evaluation of primary cancer, while PET/CT showed a slightly higher detection rate for axillary lymph node than scintimammography. According to the biological pattern, SUVmax and SUVavg resulted significantly different among histological subtypes, whereas scintimammographic data did not. At the end of neo-adjuvant therapy, pathological complete response was obtained in 12 (24.4%) patients, while 37 had a partial or no response to NST (identified as no-responders). On the basis of histopathological response to NST, median WOI resulted significantly lower in responders than non-responders (30.5% vs. 44%; P=0.027). Conversely, SUVmax and SUVavg were significantly higher in responders than non-responders (all P<0.05). In this latter subset of patients, high WOTs were associated with low SUVs. On the contrary, in responder group, high SUVs were reported particularly for high WOT values. CONCLUSIONS Scintimammography with sestamibi did not accurately determine the responsiveness to therapy. FDG PET/CT is more accurate in the prediction of response to therapy, particularly in the aggressive LABC subtype. Moreover, semiquantitative data by FDG PET seems to be linked with the chemosensitivity to NST.

Correlation between cancer antigen 15.3 value and qualitative and semiquantitative parameters of positron emission tomography/computed tomography in breast cancer patients

BACKGROUND The association of PET/CT and tumor markers can be considered complementary, since any significant increases of tumor markers can indicate the presence of disease while PET/CT is able to detect and describe the tumor sites. In this retrospective, single-institution study, we determine the correlation between cancer antigen (CA) 15.3 value and qualitative and semi-quantitative PET/CT data in breast cancer (BC) patients. METHODS 193 BC patients (median age 61 yrs) already treated with primary treatment (surgery and others) were identified through institutional databases. All patients underwent PET/CT for increase in tumor markers, post-therapy evaluation, restaging and doubtful conventional imaging for disease relapse. The CA15.3 values before PET/CT scan were collected for all patients. Clinical outcome was defined as presence or absence of disease recurrence based on follow-up data (histological or imaging findings). CA15.3 quartile values and qualitative and semi-quantitative (maximum Standardized Uptake Value - SUVmax) PET/CT findings were compared with chi-square test and linear regression analysis. RESULTS The mean value of CA15.3 was significantly higher in patients with positive than negative PET/CT (67.51±120.92 vs. 25.54±17.54, p<0.005). PET/CT was positive in 107 (55%) and negative in 86 (45%) patients; CA15.3 value was considered abnormal (≥ 31 UI/mL) in 85 (44%) patients; 57 of them showed positive PET/CT while 28 a negative scan (67 vs. 33%, p<0.05). In all 193 patients, the disease recurrence was found in 71 (37%), whereas 122 (63%) were disease-free. The diagnostic accuracy of PET/CT in all 193 patients was 74%. Among patients with normal CA15.3 value (n=108), 50 showed positive PET/CT; 24 out of these latter 50 patients (48%) had recurrence of disease. The combination of the highest quartile of CA15.3 (value>45 UI/ml) and FDG PET/CT determined high sensitivity and accuracy (92% and 82%, respectively) but a low specificity (50%) for restaging BC patients. The highest specificity (~ 70%) was found when PET/CT and 2nd quartile of CA15.3 (value: 12.95-25) were associated. No correlation between CA15.3 values and SUVmax was found (p=0.489); whereas a trend in increase of the CA15.3 value and SUVmax in the presence of visceral and no-visceral site of disease (22.4±16.2, 64.9±108 and 6.4±4.2, 8.2±5.1, respectively) was identified. CONCLUSIONS The value of CA15.3 and PET/CT findings are consistently complementary. About 25% of BC patients with a negative CA15.3 value had a positive PET/CT and disease relapse. SUVmax and CA15.3 values are not correlated.

Diagnostic and prognostic impact of fluorine-18-fluorodeoxyglucose PET/CT in preoperative and postoperative setting of breast cancer patients

Purpose The aim of this study was to assess the diagnostic and prognostic value of fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT in patients with breast cancer (BC) in the preoperative and the postoperative setting. Patients and methods Between 2011 and 2015, we prospectively enrolled 275 patients (mean age: 53 years) with BC (stage I–III; triple-negative or HER2-positive cancer). One-hundred and forty-nine (54.2%) patients underwent 18F-FDG PET/CT before neoadjuvant therapy and 126 (45.8%) after surgery and before any additional adjuvant therapy. The patients were followed for a median period of 44 (2–57) months. The different effects of PET/CT on the presetting and postsetting phase form a therapeutic and prognostic point of view were assessed by &khgr;2, by Kaplan–Meier, and Cox-regression analyses. Results In the preoperative setting, PET/CT provided additional diagnostic information in 42/149 (28%) patients. In particular, 17/70 (24%) patients at stage III were converted into stage IV and 4/68 (6%) at stage II were upstaged to IV. In the postoperative setting, PET/CT upstaged the disease in both stage IIIC and stage IV in 14/126 (11%) cases. At the end of follow-up, 28/271 (10%) patients died from BC and 40 (15%) had a recurrence of disease. On Kaplan–Meier analysis, patients with a positive PET/CT other than the primary tumor site showed both a worse overall survival and a worse disease-free survival compared with their counterpart (76 vs. 92%; P=0.063 and 65 vs. 100%; P<0.001). Conversely, in the postoperative setting, no differences in overall survival and disease-free survival were found between patients with positive and negative PET/CT findings (both P>0.05). On multivariate Cox-regression analysis, a positive PET/CT was a significant predictive factor of a poor prognosis in the preoperative setting. The significance was lost in the postoperative setting. Conclusion In the preoperative setting, PET/CT can provide additional diagnostic and prognostic information. Conversely, in the postoperative setting, PET/CT adds diagnostic information, but does not provide any adjunctive prognostic assessment.

Aromatase inhibitors as neoadjuvant treatment in elderly patients with locally advanced breast cancer

Pre-operative volume reduction of locally advanced breast cancers (LABC) is an issue of great importance when approaching elderly women, who often present with extensive disease along with a burden of co-morbidity which increases the risk of complications and mortality from treatment. A comprehensive geriatric evaluation is a necessary requirement before recommending any treatment in older patients. Endocrine treatment in the neoadjuvant setting allows disease control and downstaging of tumours and is fairly well tolerated. Tamoxifen has been the mainstay of endocrine therapy for patients unable to undergo surgery, but resistance eventually develops. Aromatase inhibitors (AIs) are superior to tamoxifen in this setting, with greater downstaging of the tumour and disease control. AIs are now the treatment of choice in elderly patients with oestrogen receptor-positive breast cancer who are being considered for neoadjuvant endocrine therapy. There are some data that definitive treatment with an AI for LABC in unfit patients may guarantee long-term control of disease.