Prognostic contribution of mammographic breast density and HER2 overexpression to the Nottingham Prognostic Index in patients with invasive breast cancer.
To investigate whether very low mammographic breast density (VLD), HER2, and hormone receptor status holds any prognostic significance within the different prognostic categories of the widely used Nottingham Prognostic Index (NPI). We also aimed to see whether these factors could be incorporated into the NPI in an effort to enhance its performance.



This study included 270 patients with newly diagnosed invasive breast cancer. Patients with mammographic breast density of <10 % were considered as VLD. In this study, we compared the performance of NPI with and without VLD, HER2, ER and PR. Cox multivariate analysis, time-dependent receiver operating characteristic curve (tdROC), concordance index (c-index) and prediction error (0.632+ bootstrap estimator) were used to derive an updated version of NPI.



Both mammographic breast density (VLD) (p < 0.001) and HER2 status (p = 0.049) had a clinically significant effect on the disease free survival of patients in the intermediate and high risk groups of the original NPI classification. The incorporation of both factors (VLD and HER2 status) into the NPI provided improved patient outcome stratification by decreasing the percentage of patients in the intermediate prognostic groups, moving a substantial percentage towards the low and high risk prognostic groups.



Very low density (VLD) and HER2 positivity were prognostically significant factors independent of the NPI. Furthermore, the incorporation of VLD and HER2 to the NPI served to enhance its accuracy, thus offering a readily available and more accurate method for the evaluation of patient prognosis.
Department of Clinical Radiology, Kuopio University Hospital, Puijonlaaksontie 2, 70210, Kuopio, PO Box PL 100, 70029, KYS, Finland. amro.masarwah@kuh.fi.
Amro
0000-0001-9687-6020
A
Masarwah
Department of Oncology, Kuopio University Hospital, Puijonlaaksontie 2, 70210, Kuopio, PO Box PL 100, 70029, KYS, Finland.|Biocenter Kuopio and Cancer Center of Eastern Finland, University of Eastern Finland, Yliopistonranta 1E, P.O.Box 1627, 70211, Kuopio, Finland.|Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1E, P.O.Box 1627, 70211, Kuopio, Finland.
Päivi
P
Auvinen
Department of Clinical Radiology, Kuopio University Hospital, Puijonlaaksontie 2, 70210, Kuopio, PO Box PL 100, 70029, KYS, Finland.
Mazen
M
Sudah
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Yliopistonranta 1E, P.O.Box 1627, 70211, Kuopio, Finland.
Vaiva
V
Dabravolskaite
Department of Clinical Radiology, Kuopio University Hospital, Puijonlaaksontie 2, 70210, Kuopio, PO Box PL 100, 70029, KYS, Finland.
Otso
O
Arponen
Department of Clinical Radiology, Kuopio University Hospital, Puijonlaaksontie 2, 70210, Kuopio, PO Box PL 100, 70029, KYS, Finland.
Anna
A
Sutela
Institute of Biomedicine, Department of Medicine, University of Eastern Finland, Yliopistonranta 1E, P.O.Box 1627, 70211, Kuopio, Finland.
Sanna
S
Oikari
Department of Pathology, Kuopio University Hospital, Puijonlaaksontie 2, 70210, Kuopio, PO Box PL 100, 70029, KYS, Finland.|Biocenter Kuopio and Cancer Center of Eastern Finland, University of Eastern Finland, Yliopistonranta 1E, P.O.Box 1627, 70211, Kuopio, Finland.|Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1E, P.O.Box 1627, 70211, Kuopio, Finland.
Veli-Matti
VM
Kosma
Department of Clinical Radiology, Kuopio University Hospital, Puijonlaaksontie 2, 70210, Kuopio, PO Box PL 100, 70029, KYS, Finland.|Biocenter Kuopio and Cancer Center of Eastern Finland, University of Eastern Finland, Yliopistonranta 1E, P.O.Box 1627, 70211, Kuopio, Finland.|Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1E, P.O.Box 1627, 70211, Kuopio, Finland.
Ritva
R
Vanninen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D000071060:Breast Density; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D016019:Survival Analysis; D047368:Tumor Burden
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases
Breast density; HER2; NPI; Nottingham prognostic index; Prediction; Prognosis