Retracted Article: Prognostic Factors in Breast Cancer: The Value of the Nottingham Prognostic Index for Patients Treated in a Single Institution

Purpose The Nottingham Prognostic Index (NPI) is used to predict survival in patients with breast cancer. This index is based on tumor size, lymph node stage, and histological grade and allows the stratification of patients into three different prognostic groups. Our aim was to verify the effect of some prognostic variables on survival and to establish the independent influence of each of these variables by a survival regression analysis. We applied the NPI to the same group of patients to assess its predictive power and reproducibility. Methods We evaluated 311 women with breast cancer treated between January 1993 and December 1998. Results In a multivariate analysis (Cox proportional hazard model), only size, lymph node involvement, and histological grade were independent prognostic factors. The survival curves obtained after applying the NPI were similar to those for the factors with independent prognostic significance derived from our multivariate analysis. Conclusion The NPI allows us to accurately predict prognosis, and we advocate its standardized use.     

Is Hormone Replacement Therapy‐Related Breast Cancer More Favorable? A Case‐Control Study

Hormone replacement therapy (HRT)-related breast cancer may carry a better prognosis since there is no increase in breast cancer deaths. We looked at the prognostic risk factors and outcome inpatients who had ever taken HRT compared to those who had not, in a case control study. Subgroups of recent-users and those using HRT for >5 years were also compared to controls. Tumor size, grade, vascular invasion, lymph node, and estrogen receptor status as well as median Nottingham Prognostic Indicator (NPI) were compared between cases and controls. Absolute survival between ever-users and never-users was compared by life table analysis. There was no difference between all the cases and their controls for the five prognostic factors. NPI in each group was also similar. Absolute survival between ever-users and never-users was not significantly different either (p = 0.678). There was no evidence that HRT-related breast cancer has a more favorable outcome.     

BS10THE PROGNOSTIC SIGNIFICANCE OF THE OVEREXPRESSION OF THE GROWTH FACTOR CRIPTO IN PATIENTS WITH BREAST CANCER

Purpose To determine the prognostic significance and long term survival of breast cancer patients with overexpression of the epidermal growth factor Cripto. Methodology 120 formalin fixed paraffin embedded breast cancer specimens were constructed on a tissue microarray and detection of Cripto carried out by immunohistochemical staining. Patients were treated between 1989 and 1995 and the median follow up was 125 months. We examined the association of Cripto positivity with age, menopausal status, grade and size of tumour, lymph node status, tumour type, ER/PR/HER2 status, Ki67 and Nottingham Prognostic Index (NPI). Results 48% of patients were Cripto positive. We demonstrated a significant association between overexpression of Cripto and NPI (p < 0.01), grade of tumour (p < 0.01), progesterone receptor (p = 0.02), Ki 67 (p = 0.02), tumour type (p = 0.04) and most importantly overall survival (p = 0.0003). Cox regression analysis revealed Cripto to be an independent prognostic variable for survival – HR 2.79 (95% CI 1.20–6.50). Conclusion Overexpression of Cripto is associated with high grade poor prognostic breast cancer and a significantly decreased patient survival. Future research is required to confirm these findings and to develop an anti‐Cripto humanised antibody for clinical use.     

Prognostic indexes in breast cancer: comparison of the Nottingham and Adelaide indexes

The search for single independent prognostic factors in breast cancer has often produced conflicting results. Therefore, prognostic indexes have been compiled by combining several parameters. In this study we compare the Nottingham Prognostic Index (NPI), which is based on traditional prognostic factors (diameter of the neoplasm, lymph node status and histological grade) with the Adelaide Prognostic Index (API), which is based on the tumour diameter and two biological parameters: oestrogen receptors and cell kinetics. We considered 82 cases of breast cancer observed over the period 1987-1990 with a minimum follow-up of 60 months. The NPI gives a better definition of the prognostic profile for each patient. Our results indicate three prognostic groups (good, moderate, unfavourable), which differ with respect to disease-free survival (DFS; P=0.0024) and overall survival (OS; P=0.0033). In contrast, the API scores showed no significant correlation with OS or DFS. The use of prognostic indexes, especially when compiled using traditional parameters, is a useful aid to the clinician, since they can provide a reliable indication of how individual tumours will evolve.     

Long-term observational follow-up study of breast cancer diagnosed in women ≤40 years old

The prognosis of young breast cancer patients has been considered to be much poorer than in older patients. Two hundred and sixty-eight premenopausal women with a median follow-up time of 74.0 months were included in the study. 33.5% had oestrogen receptor-negative and 34.6% progesterone receptor-negative tumours. 15.2% of the tumours were HER2-positive. Five-year breast cancer-specific survival (BCSS) was 81.1% and the corresponding 10-year figure was 72.3%. 91.8% of all relapses occurred within seven years of surgery. Among the ≤35-year-old women, only 2 of 38 (5.3%) relapsed beyond seven years of follow-up. Lymph node ratio was the most significant independent prognostic factor of poor disease-free survival and BCSS. This study revealed a high relapse rate in the youngest women as early as during the first few years after diagnosis, although their prognosis as a whole was surprisingly good.     

Breast cancer in women aged 35 and under: prognosis and survival

BACKGROUND: Breast cancer comprises 22% of all cancers occurring in females but only 2% of cases occur in women aged 35 years and less. The presentation, behaviour and prognosis of breast cancer in such women, when compared with older women, are unclear and conflicting results have been reported. This study has audited clinical and pathological features in patients aged 35 years and under with breast cancer. METHODS: One hundred and thirteen patients were identified. The details of clinical staging, local and distant disease recurrence and overall survival were obtained for all patients. Histological sections of tumours were examined for type, grade, size, presence of surrounding intraductal carcinoma, presence of vascular space invasion, lymph node involvement and oestrogen receptor (ER) status. RESULTS: Histological examination of the tumours revealed that 94% were invasive ductal carcinoma. In 73% of the cases the tumours were grade 3, 49% of patients who underwent axillary surgery had lymph node involvement and 20% of tumours expressed ERs. The overall 5-year survival was 64%. Predictors of a poorer survival (univariate analysis) were: increasing tumour size, absence of ERs, presence of lymphovascular space invasion, axillary lymph node involvement and detectable metastases at the initial presentation. Multivariate analysis revealed that only lymphovascular space invasion was an independent predictor of a poor survival. CONCLUSION: Breast cancer in young (< or = 35 years) women is biologically aggressive, compared with older women. Factors predicting survival and overall survival rates, however, were comparable with those previously reported for older women with breast cancer.     

Is age at diagnosis an independent prognostic factor for survival following breast cancer?

BACKGROUND: Previous studies of patients with breast cancer have examined age at diagnosis as a prognostic factor for survival with contradictory results. The current study examines the effect of age in conjunction with pathological tumour size, lymph node status and histological grade to clarify whether age at diagnosis is an independent factor for overall survival. METHODS: This is a population-based study that examines the survival of 393 women with a first diagnosis of breast cancer in 1992 in the Greater Western region of Sydney in New South Wales, Australia. Survival analysis was conducted using the Kaplan-Meier method. Relative risks associated with age at diagnosis, pathological tumour size, and number of positive lymph nodes and histological grade and adjusted for each other were computed using Cox proportional hazard regression. Patients' ages were categorized as 'younger' (<40 years of age at diagnosis), 'middle-aged' (40-69 years) or 'older age' (>69 years). RESULTS: The 10-year survival of women <40 years was 49%, which was significantly lower than 'middle-aged' women (73%). For women with node-negative breast cancer, younger women had a significantly (P = 0.011) poorer survival rate (68%) than middle-aged (90%) or older women (80%). After adjusting for the effects of the pathological tumour size, the lymph node status and histological grade, women <40 years showed a higher risk of dying than older women. However, young women detected with a small (<20 mm) node-negative tumour have a good prognosis. CONCLUSIONS: Age at diagnosis, tumour size and lymph node status were independent prognostic indicators for survival. Age at diagnosis should be considered as an important factor in making decisions about adjuvant therapy, irrespective of nodal status.     

Prognostic Factors for Metachronous Contralateral Breast Cancer: Implications for Management of the Contralateral Breast

The absolute number of breast cancer survivors who are at risk for metachronous contralateral breast cancer (mCBC) has dramatically increased. The objectives of this study were to identify factors predictive of survival for patients with mCBC and to determine clinicopathological factors predictive of advanced mCBC. Using the Surveillance, Epidemiology, and End Results data base, we identified women, ages 18–80, diagnosed with invasive breast cancer from 1992 to 2010. We excluded patients with bilateral and stage IV primary breast cancer. Patients who developed mCBC ≥12 months from initial diagnosis were identified. Kaplan–Meier methods and Cox proportional hazards modeling were used to determine survival of patients with mCBC. Multivariate logistic regression was utilized to determine factors associated with advanced mCBC. We identified 6,673 patients who developed mCBC during our study period. The median interval between initial breast cancer and mCBC was 5 years. The strongest predictor of overall survival was the nodal status of the mCBC. Other significant prognostic factors included patient age; race; size, nodal status, estrogen receptor status, grade, and type of surgery of the initial breast cancer; grade of the mCBC; and use of radiation therapy for the mCBC. Overall, 25% of mCBCs were node positive. Younger age, black race, and characteristics of the initial breast cancer (increased size, invasive lobular histology, mastectomy treatment, and node‐positivity) were significantly associated with node‐positive mCBC (all p < 0.0.05). The most powerful predictor of survival for patients with mCBC is the nodal status of mCBC. Patients with advanced initial breast cancers are more likely to develop node‐positive mCBC. Adherence to current surveillance and adjuvant therapy guidelines may minimize the risk and mortality of mCBCs.     

Breast size and prognosis in early breast cancer.

The influence of breast size on the prognosis of 196 patients with early breast cancer diagnosed in the period 1984-1985 was studied. Breast size was based on the volume from mammography. This method was validated against the volume of the mastectomy specimen determined by water displacement in 18 patients and found to be accurate (r = 0.93, P < 0.01). The median breast volume was 833.5 cm3 (interquartile range 522.8-1153.3 cm3). Breast size was significantly associated independently with age (Spearman's rank r = 0.24. P = 0.001), menstrual status (z = -4.81, P < 0.001), body weight (Spearman's rank r = 0.61, P < 0.001), T stage (z = -1.91, P = 0.05) but not N stage (z = -1.64, P = 0.10) or hormone receptor status (z = -0.80, P = 0.42). In an analysis of breast size and other known prognostic factors, based upon Cox's proportional hazards regression, N stage was the only significant factor for both breast cancer survival and disease-free survival. Even though women with larger tumours at presentation had larger breasts, breast size was not a significant prognostic factor in early breast cancer.     

Prognostic significance of the DNA content of human breast cancer

The DNA content of paraffin embedded primary tumour tissue has been measured by flow cytometry in 354 patients with operable breast cancer. Tumour ploidy significantly correlated with tumour size, histological grade, and with menopausal status. No significant correlation with oestrogen receptor status or lymph node involvement was found. Patients with diploid cancers had a significantly improved short term survival and disease-free interval (DFI) compared with patients having aneuploid tumours. However, no difference in survival or DFI was shown after longer term follow-up (median 84 months). Multivariate analysis showed no independently significant prognostic value for tumour ploidy. No patient in this study received adjuvant therapy.     

Prognostic significance of oestrogen and progestogen receptor activities in breast cancer

The prognostic significance of the tumour activities of 2 steroid receptors, those for oestrogen (ER) and for progestogen (PgR), has been studied in 372 patients with breast cancer, in whom follow-up was available for 2-6 years (median 41 months). Of 252 patients with operable disease, 75.8 per cent had ER-positive tumours and 46.4 per cent had PgR-positive tumours, though a small additional fraction (6.3 per cent) had an equivocal PgR assay result. For the 236 patients with unequivocal receptor status, the relationships between disease-free interval or overall survival and receptor activity and other factors were evaluated by univariate and multivariate analyses. The latter revealed that only tumour size, node status, menstrual status and ER status related significantly to both disease-free interval and survival, though adjuvant therapy also related to disease-free interval, and tumour grade related to survival. It is concluded that measurements of PgR activity do not add to the prognostic significance of ER status.     

Estrogen and Progesterone Receptors in Primary Breast Cancer

Abstract: The purpose of this study was to determine biological variable profiles and survival experiences associated with different combinations of estrogen receptor (ER) and progesterone receptor (PR) status (ER+PR+, ER+PR-, ER-PR+, ER-PR-). Data were collected and provided by the State Health Registry (SHR) of Iowa, part of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Significant associations were determined for individual prognostic variables with each ER/PR categories, and overall survival was compared between each ER/PR category. Multiple logistic regression analyses were conducted to determine all significant prognostic variables associated with each ER/ PR category. All women diagnosed with primary breast cancer in Iowa from 1990 through 1992 were included in this study (N = 6, 178). In unadjusted analyses, Caucasian woman and older women were significantly more likely to be ER + PR+, while African American women and younger women were significantly more likely to be ER-PR-. In multivariate analyses, each ER/PR category was associated with distinct profile of age, menopausal status, histologic grade, and histology. Survival was best for women in the ER+PR+ group, followed, in decreasing order, by ER+PR-, ER-PR+, and ER-PR-. In this population-based study of primary breast cancer, combined hormone receptor status was a significant prognostic determinant for primary breast cancer, and was associated with distinct biological variables and survival experiences. In combination with other variables such as age, menopausal status, tumor histologic grade, and tumor histology, combined hormone receptor status can provide important prognostic information to the clinician.?     

Oestrogen receptors revisited: long-term follow up of over five thousand breast cancer patients

BACKGROUND: The oestrogen receptor status of a breast tumour predicts the response to hormonal treatment and is an important prognostic marker; women with oestrogen receptor positive tumours having a better short-term survival outcome. METHODS: Kaplan-Meier estimates and Cox proportional hazard model were used to estimate the association between oestrogen receptor levels and long-term breast cancer-specific survival outcomes in 5735 women diagnosed with breast carcinoma from 1970 to 1997 in Western Australia. Further analysis was performed on a subset of women for whom biochemical and tumour characteristics were also available. RESULTS: Five-year breast cancer-specific survival estimates for women with oestrogen receptor positive tumours was 0.85 (95% CI 0.84-86) compared to 0.72 (95% CI 0.70-74) for women with oestrogen receptor negative tumours. The relative survival advantage of an oestrogen positive tumour over oestrogen negative tumours disappeared by the fourth year (0.8, 95% CI 0.6-1.0). Conditional upon surviving 5 years, long-term breast cancer-specific survival was better for women with oestrogen receptor and progesterone receptor negative tumours compared to other women (log rank test P-value <0.05). CONCLUSION: Despite an earlier survival advantage for women diagnosed with oestrogen receptor positive tumours, after 5 years of survival, women with oestrogen receptor negative and progesterone receptor negative tumours had better long-term survival outcomes from breast cancer compared to other women.     

Correlation between Blood Flow Signal of Color Flow Imaging and Nottingham Prognostic Index in Patients with Breast Carcinoma

BACKGROUND: The purpose of this study was to investigate the relationship between blood supply detected by Doppler ultrasound and the Nottingham Prognostic Index (NPI) in breast cancer patients. PATIENTS AND METHODS: 137 patients with breast carcinoma, who had undergone color Doppler flow imaging (CDFI) and surgery, were involved in this retrospective study. CDFI was divided into 4 levels: absent (grade 0), minimal (grade 1), moderate (grade 2), and marked (grade 3). NPI was calculated as: NPI = 0.2 × tumor size (cm) + grade (I-III) + lymph node score (1-3). All patients were followed until the final observation (July 2010), or until the time of death. The survival state of the patients was divided into 3 categories: healthy survival, metastasis, and death. RESULTS: Blood signal grades were positively correlated with NPI (Spearman r = 0.55926, p < 0.0001) and survival state (χ(2) = 9.0248, p < 0.01). Patients with abundant blood flow signal (grade 2-3) had a significantly shorter overall survival than did those with limited blood flow signal (grade 0-1) (χ(2) = 5.0384, p = 0.0248). CONCLUSION: Flow signal measured by Doppler ultrasound may be useful as a prognostic indicator for patients with breast carcinoma.     

Breast cancer in young Asian women: study on survival

BACKGROUND: Breast cancer in young patients is often associated with a poorer prognosis, but there has been a paucity of published data in an Asian population. METHODS: One hundred and six patients (12.6%) under the age of 40 years with breast cancer (group V) were compared with 737 patients with breast cancer aged 40 years or more (group W). Demographics, presentations, pathological profiles, treatment and survival measures were analysed. RESULTS: Median tumour size was similar in both groups. Group V had more patients with grade 3 tumours and nodal involvement compared to group W (51.5% vs 38.1%, P = 0.012 and 52.5% vs 41.8%, P = 0.045). The mean Nottingham prognostic index (NPI) score was significantly higher in group V compared to group W (4.75 vs 4.26, P < 0.001). The incidences of chemotherapy and radiotherapy in group V were higher than group W (69.2% vs 35.2%, P < 0.001 and 41.1% vs 24.4%, P = 0.002). There were no differences in overall survival and disease-free survival (local recurrence). CONCLUSION: Patients below 40 years with breast cancer have tumours with a poorer prognostic profile. However, this did not translate into a poorer overall survival, and this might be attributable to more aggressive adjuvant treatment of younger patients.     

Consequences of axillary recurrence after conservative breast surgery

BACKGROUND: The aim was to study the incidence, time course and prognosis of patients who developed axillary recurrence after breast-conserving surgery, and to evaluate possible risk factors for axillary recurrence and prognostic factors after axillary recurrence. METHODS: In a population-based cohort of 6613 women with invasive breast cancer who had breast-conserving surgery between 1981 and 1990, 92 recurrences in the ipsilateral axilla were identified. Risk factors for axillary recurrence were studied in a case-control study nested in the cohort, and late survival was documented in the women with axillary recurrence. RESULTS: The overall risk of axillary recurrence was 1.0 per cent at 5 years and 1.7 per cent at 10 years. The risk of axillary recurrence increased with tumour size (P = 0.033) and was highest in younger women (odds ratio (OR) 3.9 for women aged less than 40 years compared with those aged 50-59 years). Radiotherapy to the breast reduced the risk of axillary recurrence (OR 0.1 (95 per cent confidence interval 0.1 to 0.4)). The breast cancer-specific survival rate after axillary recurrence, as measured from primary treatment, was 78.0 per cent at 5 years and 52.3 per cent at 10 years. Tumour size and node status had a statistically significant effect on death from breast cancer. CONCLUSION: Axillary recurrence is rare, although more common in younger women with large tumours. Radiotherapy to the breast was protective. Tumour size and node status were the most important prognostic factors in women with axillary recurrence.     

Node negative breast cancer: the prognostic value of DNA ploidy for long-term survival.

The DNA content of breast tumours from 170 patients who presented between 1978 and 1980 was measured by flow cytometry. The relationship between tumour ploidy and disease outcome was assessed and its association with other prognostic factors evaluated. Compared with those with diploid tumours, patients with aneuploid tumours had significantly earlier relapse and shorter survival (P less than 0.0001). Tumour ploidy was strongly related to grade (P less than 0.001), but there was no significant association between DNA ploidy and c-erb-B-2 expression, lymph node status or tumour size. In lymph node negative and c-erb-B-2 negative patients, aneuploid tumours were associated with a poorer prognosis (P less than 0.001) than diploid tumours. Multivariate analysis showed that tumour ploidy gave independent information on disease free and overall survival. Tumour ploidy may be used as an independent prognostic variable in patients with breast cancer and it may be helpful in defining patients within the node negative or c-erb-B-2 negative groups likely to have a poor outcome who might benefit from adjuvant treatment.     

The Nottingham Prognostic Index: five- and ten-year data for all-cause Survival within a Screened Population

Introduction

The Nottingham Prognostic Index (NPI) is an established prognostication tool in the management of breast cancers (BCs). Latest ten-year survival data have demonstrated an improved outlook for each NPI category and the latest UK five- and ten-year survival from BC has been reported to be 85% and 77%, respectively. We compared survival of each NPI category for BCs diagnosed within the national breast screening service in Wales (Breast Test Wales (BTW)) to the latest data, and reviewed its validity in unselected cases within a screened population.

Methods

All women screened between 1998 and 2001 within BTW were included. The NPI score for each cancer was calculated using the size, nodal status, and grade of the primary tumour. Survival data (all-cause) were calculated after ten years of follow-up.

Results

In the three-year screening period, 199,082 women were screened. A total of 1,712 cancers were diagnosed, and 1,546 had data available for calculating the NPI. Overall five-year and ten-year survival was 94% and 82%, respectively.

Conclusions

Overall five-year and ten-year survival (all-cause) has improved even when compared with UK data for BC-specific survival. We found that the NPI remains valid for BC treatment, and that our data provide a reference for updating the all-cause survival of women diagnosed with BCs within a screened population.     

Expression and clinical significance of apolipoprotein D in male breast cancer and gynaecomastia.

BACKGROUND: Apolipoprotein D (Apo D) is a protein component of the human plasma lipid transport system which is present in benign and malignant human breast tissues. This study analysed the expression of Apo D in men with gynaecomastia or breast cancer, and evaluated its use as a prognostic marker in breast cancer. METHODS: Immunohistochemical expression of Apo D was examined in specimens from 15 men with gynaecomastia, two with in situ breast carcinoma and 68 with invasive male breast cancer. Median follow-up in patients with breast cancer was 44 months. RESULTS: All gynaecomastia specimens, both in situ carcinomas and 57 invasive carcinomas (84 per cent) stained positively for Apo D. Apo D values were significantly correlated with axillary node involvement and histological grade of the tumours. In men with breast cancer univariate analysis showed a statistical association between node status and Apo D content with relapse-free survival (P < 0.001) and overall survival (P < 0.05). Cox multivariate analysis showed that Apo D was a significant indicator of relapse-free survival (P = 0. 0089), but node status was the strongest factor able to predict both relapse-free (P = 0.0336) and overall (P = 0.0346) survival. CONCLUSION: Apo D was expressed in gynaecomastia and a high percentage of male breast carcinomas. There was a positive association of Apo D content in male breast tumours with favourable outcome. Apo D expression was a significant independent indicator of relapse-free survival in male breast cancer.     

A 13-year follow-up of patients with breast cancer presenting to a District General Hospital breast unit in southeast England

The purpose of this clinical cohort study was to examine long-term survival in groups of screen-detected and symptomatic breast cancer patients attending a specialist breast unit, and to determine the factors affecting this survival. A total of 3239 breast cancer cases (1252 screen-detected and 1987 symptomatic) diagnosed between 1989 and 2002 were followed up until the end of 2002, and breast cancer-specific survival was examined in the screened and symptomatic groups, in relation to patient age, tumour size, nodal status and histological grade. Long-term survival in this clinical cohort was high. Relative survival values in the symptomatic group were similar to population-based estimates for southeast England derived from data held at the Thames Cancer Registry, whilst survival values in the screening group were 11-12 percentage points higher at 4 years after diagnosis and onwards. Ten-year relative survival estimates were 88% in the screening group and 77% in symptomatic cases. In groups of comparable age, the difference in breast cancer-specific survival at 10 years was 19 percentage points. Survival was significantly related to tumour characteristics (size, nodal status and grade), but not to morphological tumour type or deprivation score of the subject. After adjustment for other factors, the difference in survival between the two groups was much attenuated and became statistically non-significant. The higher survival seen in the screening group can be almost entirely accounted for in terms of the detection of early stage and lower grade tumours which screening provides.