Factors influencing local control in patients undergoing breast conservation surgery for ductal carcinoma in situ.

BACKGROUND: The aim of our study was to assess various predictors for local recurrence (LR) in patients undergoing breast conservation surgery (BCS) for ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: An audit was performed of 582 consecutive patients with DCIS between Jan 1975 to June 2008. In patients undergoing BCS, local guidelines reported a margin of ≥10 mm during the above period. Guideline with regard to margin of excision changes soon after this period. We retrospectively analysed clinical and pathological risk factors for local recurrence in patients undergoing BCS. Statistical analysis was carried out using SPSS version 19, and a cox regression model for multivariate analysis of local recurrence was used. RESULTS: Overall 239 women had BCS for DCIS during the above period. The actuarial 5-year recurrence rate was 9.6%. The overall LR rate was 17% (40/239. LR was more common in patients ≤50 years: (10/31 patients, 32%) compared to patients > 50 years (30/208, 14%, P = 0.02). Forty three per cent of patients (6/14) with <5 mm margin developed LR which was significantly higher compared to patients with 5-9 mm margin (12%, 3/25) and with ≥10 mm margin (14%, 27/188, P = 0.01). On multivariate analysis age ≤50 years, <5 mm pathological margin were independent prognostic factors for local recurrence. CONCLUSION: Our study shows that younger age (≤50 years) and a margin < 5 mm are poor prognostic factors for LR in patients undergoing breast conservation surgery for DCIS.

A study of ductal versus non-ductal invasive breast carcinomas in older women: long-term clinical outcome and comparison with their younger counterparts.

Ductal carcinoma is the commonest histological type found in invasive breast carcinomas and may be associated with worse prognosis, when compared to non-ductal carcinoma. Older patients tend to display more favourable tumour biology than younger patients. This study aimed to investigate the significance of histological type and its relationship with clinical outcome in the older group. A total of 808 older (≥70 years) women with early operable primary breast cancer underwent surgery as their primary treatment, followed by optimal adjuvant therapies, in the Nottingham Breast Unit between 1973 and 2009. The histological types of the surgical specimens were reviewed and compared with those in a previously characterised younger (<70 years) series (N = 1,733), in terms of distribution and correlation with clinical outcome. Ductal type was associated with a significantly worse clinical outcome when compared to non-ductal type in the older group in terms of 10-year rates of metastasis-free survival (75 vs 79 %, p = 0.028) and overall survival (44 vs 52 %; p = 0.015). Similar worse clinical outcome was found with the ductal type in the younger group in terms of 10-year rates of metastasis-free survival (65 vs 79 %; p = 0.001) and overall survival (60 vs 78 %; p = 0.001). For all patients with ductal type carcinomas, the older series showed significantly better 10-year metastasis-free survival (75 vs 65 %, p < 0.001) and breast cancer-specific survival (75 vs 69 %, p = 0.025) when compared to the younger series. In both old and the young, ductal cancers were associated with poor survival outcome when compared to non-ductal cancers. When compared to their younger counterparts, older patients with ductal type carcinomas had better metastasis-free and breast cancer-specific survival rates (their lower overall survival was likely to be due to death from other causes), despite having a lower likelihood of receiving adjuvant systemic therapy.

Biology of primary breast cancer in older women treated by surgery: with correlation with long-term clinical outcome and comparison with their younger counterparts.

BACKGROUND: As age advances breast cancer appears to change its biological characteristics, however, very limited data are available to define the precise differences between older and younger patients. METHODS: Over 36 years (1973-2009), 1758 older (≥70 years) women with early operable primary breast cancer were managed in a dedicated clinic. In all, 813 underwent primary surgery and 575 good quality tumour samples were available for biological analysis. The pattern of biomarkers was analysed using indirect immunohistochemistry on tissue microarrays. Comparison was made with a previously characterised series of younger (<70 years) patients. RESULTS: There was high expression of oestrogen receptor (ER), PgR, Bcl2, Muc1, BRCA1 and 2, E-cadherin, luminal cytokeratins, HER3, HER4, MDM2 and 4 and low expression of human epidermal growth factor receptor (HER)-2, Ki67, p53, EGFR and CK17. Oestrogen receptor and axillary stage appeared as independent prognostic factors. Unsupervised partitional clustering showed six biological clusters in older patients, five of which were common in the younger patients, whereas the low ER luminal cluster was distinct in the older series. The luminal phenotype showed better breast cancer-specific survival, whereas basal and HER2-overexpressing tumours were associated with poor outcome. CONCLUSION: Early operable primary breast cancer in older women appears as a distinct biological entity, with existence of a novel cluster. Overall older women showed less aggressive tumour biology and ER appeared as an independent prognostic factor alongside the time-dependent axillary stage. These biological characteristics may explain the differences in clinical outcome and should be considered in making therapeutic decisions.

Radiotherapy or tamoxifen after conserving surgery for breast cancers of excellent prognosis: British Association of Surgical Oncology (BASO) II trial.

BACKGROUND: The incidence of local recurrence (LR) after conservative surgery for early breast cancer without adjuvant therapy is unacceptably high even with favourable tumours. The aim of this study was to examine the effect of adjuvant therapies in tumours with excellent prognostic features. METHODS: Patients with primary invasive breast cancer <2 cm diameter, grade 1 or good prognosis special type, and node negative, treated by wide local excision (WLE) with clear margins were randomised into a 2 × 2 clinical trial of factorial design with or without radiotherapy and with or without tamoxifen. Trial entry was allowed to either comparison or both. FINDINGS: The actuarial breast cancer specific survival in 1135 randomised patients at 10 years was 96%. Analysis by intention to treat showed that LR after WLE was reduced in patients randomised to radiotherapy (RT) (HR 0.37, CI 0.22-0.61 p<0.001) and to tamoxifen (HR 0.33, CI 0.15 - 0.70 p<0.004). Actuarial analysis of patients entered into the four-way randomisation showed that LR after WLE alone was 1.9% per annum (PA) versus 0.7% with RT alone and 0.8% with tamoxifen alone. No patient randomised to both adjuvant treatments developed LR. Analysis by treatment received showed LR at 2.2%PA for surgery alone versus 0.8% for either adjuvant radiotherapy or tamoxifen and 0.2% for both treatments. CONCLUSIONS: Even in these patients with tumours of excellent prognosis, LR after conservative surgery without adjuvant therapy was still very high. This was reduced to a similar extent by either radiotherapy or tamoxifen but to a greater extent by the receipt of both treatments.

Radiotherapy as sole adjuvant treatment for older patients with low-risk breast cancer.

Partly as a result of screening, increasing numbers of older patients are presenting with 'low risk' breast cancer: tumours from which the likelihood of breast cancer death is minute; even so, these patients have a measurable risk of local recurrence if conservative surgery is not followed by some form of adjuvant treatment. However, it must be acknowledged that any such treatment has no detectable impact upon survival, and the value of all such interventions must be considered in the context of the individual patient's non-cancer life expectancy and the complex psychosocial factors that affect older patients. If no impact on survival can be expected and the risk of local recurrence is high enough to warrant some post-operative treatment, the most powerful agent in this respect is radiotherapy. Whilst adjuvant endocrine treatment is becoming increasingly accepted as monotherapy in low risk patients, we propose that radiotherapy should not be forgotten as an alternative which, with its attendant benefits of shorter duration and high compliance, may be more suitable for a number of patients.

Beam angle manipulation to reduce cardiac dose during breast radiotherapy.

OBJECTIVE: Standard tangential radiotherapy techniques after breast conservative surgery (BCS) often results in the irradiation of the tip of the left ventricle and the left anterior descending coronary artery (LAD), potentially increasing cardiovascular morbidity. The importance of minimising radiation dose to these structures has attracted increased interest in recent years. We tested a hypothesis that in some cases, by manipulating beam angles and accepting lower-than-prescribed doses of radiation in small parts of the breast distant from the surgical excision site, significant cardiac sparing can be achieved compared with more standard plans. METHODS: A sample of 12 consecutive patients undergoing radiotherapy after left-sided BCS was studied. All patients were planned with a 6 MV tangential beam, beam angles were manipulated carefully and if necessary lower doses were given to small parts of the breast distant from the surgical excision site to minimise cardiac irradiation ("institutional" plan). Separate "hypothetical standard" plans were generated for seven patients using set field margins that met published guidelines. RESULTS: In seven patients, the institutional plans resulted in lower doses to the LAD and myocardium than the hypothetical standard plans. In the other five patients, LAD and myocardial doses were deemed minimal using the hypothetical standard plan, which in these patients corresponded to the institutional plan (the patients were actually treated using the institutional plans). CONCLUSION: Much attention has been devoted to ways of minimising cardiac radiation dose. This small sample demonstrates that careful manipulation of beam angles can often be a simple, but effective technique to achieve this.

Long-term (37 years) clinical outcome of older women with early operable primary breast cancer managed in a dedicated clinic.

BACKGROUND: A dedicated clinic for older women with early primary breast cancer, established in 1973, has recently evolved into a combined surgical/oncology facility. This study aimed to compare the clinical outcome across these periods. METHODS: From 1973 to 2010, 1758 women were managed. Analysis was carried out based on retrospective review and continued update of patient records. RESULTS: In the recent decade, 56.3% had surgery, followed by primary endocrine therapy (PET; 41.1%) and primary radiotherapy (1.5%). Before 1999, 42.8%, 55.6% and 1% of patients had surgery, PET and primary radiotherapy, respectively. The use of adjuvant endocrine therapy and radiotherapy has increased from 33.6% to 54.9% and 5.8% to 34.6%, respectively. A significant improvement was seen in the annual rates of local (2.2% versus 0.5%, P < 0.001), regional (1.8% versus 0.4%, P < 0.001) and distant (2.9% versus 1.9%, P = 0.002) recurrences. Similarly, the 5-year breast cancer-specific and overall survival rates showed improvement [81% versus 91% (P < 0.001) and 56% versus 71% (P < 0.001), respectively]. CONCLUSIONS: In the recent decade, while surgery became the predominant treatment, a significant proportion of patients had non-operative therapies, selection of which was based on multidisciplinary assessment in the clinic. This management approach appears to produce excellent clinical outcome, which is significantly better than that in earlier period.

Optimising the management of primary breast cancer in older women - a report of a multi-disciplinary study day.

PURPOSE: The objectives of the study day were to (i) develop an in-depth understanding around the biology and treatment options; (ii) explore the specific physical and psychosocial needs and consideration including patients perspective; and (iii) gain insight into the development of a dedicated, holistic and multi-disciplinary clinic service and the importance of supporting research, for older women with primary breast cancer. DESIGN: The format included presentations (with lectures from external and local faculty, and short research papers from Nottingham) with a number of interactive discussions, and sharing of patients' experience. RESULTS: Four sessions were held covering (i) pathological features, (ii) role of radiotherapy and adjuvant chemotherapy, (iii) role of surgery, geriatric assessment and quality of life issues, and (iv) challenges in running research trials. CONCLUSIONS: A dedicated and joint team approach is required to improve clinical service and support research, in order to optimise the management of primary breast cancer in older women.

Long-term clinical outcome of oestrogen receptor-positive operable primary breast cancer in older women: a large series from a single centre.

INTRODUCTION: A Cochrane review of seven randomised trials (N=1571) comparing surgery and primary endocrine therapy (PET) (oestrogen receptor (ER) unselected) shows no difference in overall survival (OS). We report outcome of a large series with ER-positive (ER+) early invasive primary breast cancer. METHODS: Between 1973 and 2009, 1065 older (≥ 70 years) women (median age 78 years (70-99)) had either surgery (N=449) or PET (N=616) as initial treatment. RESULTS: At 49-month median follow-up (longest 230 months), the 5-year breast cancer-specific survival (BCSS) and OS were 90 and 62%, respectively. Majority (74.2%) died from causes other than breast cancer. The rates (per annum) of local/regional recurrence (<1%) (following surgery), contralateral tumour (<1%) and metastases (<3%) were low. For patients on PET, 97.9% achieved clinical benefit (CB) at 6 months, with median time to progression of 49 months (longest 132 months) and significantly longer BCSS when compared with those who progressed (P<0.001). All patients with strongly ER+ (H-score >250) tumours achieved CB and had better BCSS (P<0.01). Patients with tumours having an H-score >250 were found to have equivalent BCSS regardless of treatment (surgery or PET; P=0.175), whereas for those with H-score ≤ 250, surgery produced better outcome (P<0.001). CONCLUSION: Older women with ER+ breast cancer appear to have excellent long-term outcome regardless of initial treatment. Majority also die from non-breast cancer causes. Although surgery remains the treatment of choice, patients with ER-rich (H-score >250) tumours tend to do equally well when treated by PET. This should be taken into account when therapies are considered.

Early primary breast cancer in the elderly - pattern of presentation and treatment.

INTRODUCTION: The incidence of primary breast cancer in elderly patients is increasing. However, little is known about their biological profile and most appropriate clinical management, as most studies have been conducted in the younger population. This study aimed to identify a profile of characteristics in elderly women with operable primary breast cancer and investigate the dynamics influencing the treatment decision-making process. METHODS: A review of 268 consecutive female patients >70 years of age, diagnosed with early operable primary breast cancer (<5 cm) over a 30-month period at the Nottingham Breast Institute, was conducted. Age, co-morbidity, cancer characteristics, treatment offered and undertaken, and reason for patient choice were recorded and analysed. RESULTS: The median age was 78 (range 70-100) years. In our study, 82% of the patients had one or more co-morbidities, with 34% of them having three or more co-morbidities. The commonest pathological diagnosis (from needle core biopsies) was invasive ductal carcinoma of no special type (76%) with histological grade 2 (64%). Majority of them were oestrogen receptor (ER)-positive (84%) and had a high histochemical (H)-score (83% with H-score >200). Most of the patients (60%) underwent primary surgical management, of which 45.4% received breast-conserving surgery. Among the patients who had breast-conserving surgery, 68% of them received adjuvant radiotherapy. When offered genuine choice in treatment options, most patients chose non-operative treatment. Patients who underwent non-operative treatment were on average seven years older and had significantly more co-morbidities than those who had surgery. CONCLUSION: The elderly population evidently have demographic and cancer characteristics distinct from their younger counterparts, with less patients receiving surgical management. Further work is underway to correlate this with their clinical outcomes and to examine the factors behind the treatment decision-making process.

Is surgery always indicated in older women with breast cancer?

Although surgery has long been considered the main form of curative treatment for breast cancer, its use in older women may not always be indicated. Whilst surgery has been shown to provide superior local control for breast cancer, there is conflicting evidence on whether surgery offers a significant improvement on overall survival in these patients. The more indolent tumour biology commonly seen in older women with breast cancer, coupled with competing causes of death may alter the goals of treatment. The differing needs of older patients should be thoroughly assessed to consider their comorbidities, functional status and quality of life. A comprehensive geriatric assessment and quality of life assessment could identify pretreatment risk factors and guide clinical decision making, improving morbidity and prognosis. Alternatives to surgery include primary endocrine therapy and primary radiotherapy. Further research is required to identify different patient or tumour factors which can be used to individualize treatment for breast cancer in older women and to develop holistic assessment tools which take into account their individual quality of life, geriatric syndromes and functional needs. A dedicated multidisciplinary-led clinic may provide a suitable platform for the assessment, review and management of this distinctive set of patients.

A vision to optimise the management of primary breast cancer in older women.

Majority of breast cancer are diagnosed at >65 years. Efforts to develop clinical service and research are spent mainly on younger patients. Little is known about the biology and long-term clinical outcome of breast cancer in the elderly. However there is data suggesting that there are differences. Knowledge related to breast cancer in the elderly is urgently needed and we need to optimise their management - not 'over' or 'under' treating them, taking into account of both physical and psychosocial dimensions. The Nottingham Breast Services established a dedicated elderly primary breast cancer service from its inception over 30 year ago, which has recently developed into a combined surgical/oncology facility. A joint effort and team approach are required in both developing clinical service and research, in order to optimise management. There is an immense need to develop a dedicated elderly breast cancer service and to support ongoing research.

Biological profile of oestrogen receptor positive primary breast cancers in the elderly and response to primary endocrine therapy.

Aromatase inhibitors have been shown to be superior to Tamoxifen in several settings. It is unclear whether this superiority extends to their use as primary endocrine therapy in elderly patients with early operable primary breast cancer. Biological characteristics of the tumours may aid in selecting the most suitable agent. Primary endocrine therapy with Anastrozole in 64 women >70 years with oestrogen receptor alpha-positive (ERalpha+) breast cancer was compared to that in 84 treated with Tamoxifen during the same period. Biomarkers were assessed by immunohistochemistry on diagnostic core biopsies. There was no significant difference between the two groups (Anastrozole vs Tamoxifen) in terms of clinical benefit rates at 6 months (97% vs 100%) or median progression free survival (16.5 vs 22.5 months). There were no withdrawals due to adverse events from Anastrozole, compared to four with Tamoxifen. 46%, 99%, 8% and 5% of all patients were positive for progesterone receptor, ERbeta2, HER2 and EGFR, respectively, and 64% of patients had a moderate Ki-67 index. Positive HER2 status (18 vs 21 months, p=0.003) and moderate Ki-67 index (17.5 vs 23 months, p=0.042) were associated with significantly shorter progression free survival. Results thus far show that primary endocrine therapy with Anastrozole in elderly patients with early operable ERalpha+ breast cancer is similar to Tamoxifen in terms of efficacy, but appears to be associated with less adverse events leading to withdrawals. In this population, ERalpha+ breast cancer also appears to have a less aggressive biological profile favouring better hormone sensitivity.

Pathological features of primary breast cancer in the elderly based on needle core biopsies--a large series from a single centre.

Most breast cancer patients are diagnosed at>65 years but research efforts are mainly focussed on younger patients. Knowledge related to elderly breast cancer is urgently needed. Patients>70 years presenting with early operable primary breast cancer were studied. Pathological features of diagnostic needle core biopsies taken from 2078 tumours from 2061 consecutive patients managed under a dedicated elderly breast cancer service, in 1987-2006, were reviewed. There were 1996 invasive carcinoma of mammary type (96%) with (N=200) or without associated ductal carcinoma in situ (DCIS); 81 were DCIS only (3.9%). One malignant adenomyoepithelioma was seen. Among the invasive carcinomas, ductal carcinoma of no special type was seen in 87.1% while lobular and mucinous features were noted in 6.9% and 3.1%, respectively. Histological grades and oestrogen receptor (ER) status were assessed respectively in 826 and 1557 invasive carcinomas. Majority were grade 2 (62.7%), followed by grade 1. Around 82% were ER-positive. Their pattern was compared with that in 2674 tumours from younger (< or =70 years) counterparts. In all age groups there was a marked biphasal distribution of ER-positivity, but in patients>70 years this distribution was more marked, with a great preponderance of highly ER-positive tumours, and a substantial minority being ER-negative, with very few in intermediate groups. We believe that this is the largest dataset of pathological features of elderly primary breast cancer from one institution. We have clearly confirmed the high frequency of ER-positive tumours in elderly patients. Further work is underway to assess long-term outcome and clinical relevance.

The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.

BACKGROUND: The international standard radiotherapy schedule for early breast cancer delivers 50 Gy in 25 fractions of 2.0 Gy over 5 weeks, but there is a long history of non-standard regimens delivering a lower total dose using fewer, larger fractions (hypofractionation). We aimed to test the benefits of radiotherapy schedules using fraction sizes larger than 2.0 Gy in terms of local-regional tumour control, normal tissue responses, quality of life, and economic consequences in women prescribed post-operative radiotherapy. METHODS: Between 1999 and 2001, 2215 women with early breast cancer (pT1-3a pN0-1 M0) at 23 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy over 5 weeks or 40 Gy in 15 fractions of 2.67 Gy over 3 weeks. Women were eligible for the trial if they were aged over 18 years, did not have an immediate reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 1105 women were assigned to the 50 Gy group and 1110 to the 40 Gy group. After a median follow up of 6.0 years (IQR 5.0-6.2) the rate of local-regional tumour relapse at 5 years was 2.2% (95% CI 1.3-3.1) in the 40 Gy group and 3.3% (95% CI 2.2 to 4.5) in the 50 Gy group, representing an absolute difference of -0.7% (95% CI -1.7% to 0.9%)--ie, the absolute difference in local-regional relapse could be up to 1.7% better and at most 1% worse after 40 Gy than after 50 Gy. Photographic and patient self-assessments indicated lower rates of late adverse effects after 40 Gy than after 50 Gy. INTERPRETATION: A radiation schedule delivering 40 Gy in 15 fractions seems to offer rates of local-regional tumour relapse and late adverse effects at least as favourable as the standard schedule of 50 Gy in 25 fractions.

The use of a commercial remote desktop program in the delineation of target volumes in radiotherapy.

Recent guidance from the Royal College of Radiologists suggests that there should be close collaboration between oncologists and radiologists in target volume determination. However, the guidance also states that there may be practical difficulties in achieving this. To ameliorate some of these difficulties, we have implemented a readily available remote desktop package, Microsoft NetMeeting, in conjunction with a commercial virtual simulation package, ProSoma. This allows radiologists to conference easily with oncologists on a particular patient, as the full functionality of the virtual simulator is available simultaneously to both parties. We have found that this solution is eminently practical and increases the amount of interaction between oncologists and radiologists during target volume definition.

The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.

BACKGROUND: The international standard radiotherapy schedule for breast cancer treatment delivers a high total dose in 25 small daily doses (fractions). However, a lower total dose delivered in fewer, larger fractions (hypofractionation) is hypothesised to be at least as safe and effective as the standard treatment. We tested two dose levels of a 13-fraction schedule against the standard regimen with the aim of measuring the sensitivity of normal and malignant tissues to fraction size. METHODS: Between 1998 and 2002, 2236 women with early breast cancer (pT1-3a pN0-1 M0) at 17 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy versus 41.6 Gy or 39 Gy in 13 fractions of 3.2 Gy or 3.0 Gy over 5 weeks. Women were eligible if they were aged over 18 years, did not have an immediate surgical reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 749 women were assigned to the 50 Gy group, 750 to the 41.6 Gy group, and 737 to the 39 Gy group. After a median follow up of 5.1 years (IQR 4.4-6.0) the rate of local-regional tumour relapse at 5 years was 3.6% (95% CI 2.2-5.1) after 50 Gy, 3.5% (95% CI 2.1-4.3) after 41.6 Gy, and 5.2% (95% CI 3.5-6.9) after 39 Gy. The estimated absolute differences in 5-year local-regional relapse rates compared with 50 Gy were 0.2% (95% CI -1.3% to 2.6%) after 41.6 Gy and 0.9% (95% CI -0.8% to 3.7%) after 39 Gy. Photographic and patient self-assessments suggested lower rates of late adverse effects after 39 Gy than with 50 Gy, with an HR for late change in breast appearance (photographic) of 0.69 (95% CI 0.52-0.91, p=0.01). From a planned meta-analysis with the pilot trial, the adjusted estimates of alpha/beta value for tumour control was 4.6 Gy (95% CI 1.1-8.1) and for late change in breast appearance (photographic) was 3.4 Gy (95% CI 2.3-4.5). INTERPRETATION: The data are consistent with the hypothesis that breast cancer and the dose-limiting normal tissues respond similarly to change in radiotherapy fraction size. 41.6 Gy in 13 fractions was similar to the control regimen of 50 Gy in 25 fractions in terms of local-regional tumour control and late normal tissue effects, a result consistent with the result of START Trial B. A lower total dose in a smaller number of fractions could offer similar rates of tumour control and normal tissue damage as the international standard fractionation schedule of 50 Gy in 25 fractions.

Survival of invasive breast cancer according to the Nottingham Prognostic Index in cases diagnosed in 1990-1999.

UNLABELLED: The Nottingham Prognostic Index (NPI) is a well established and widely used method of predicting survival of operable primary breast cancer. AIMS: Primary: To present the updated survival figures for each NPI Group. Secondary: From the observations to suggest reasons for the reported fall in mortality from breast cancer. METHODS: The NPI is compiled from grade, size and lymph node status of the primary tumour. Consecutive cases diagnosed and treated at Nottingham City Hospital in 1980-1986 (n=892) and 1990-1999 (n=2,238) are compared. Changes in protocols towards earlier diagnosis and better case management were made in the late 1980s between the two data sets. RESULTS: Case survival (Breast Cancer Specific) at 10 years has improved overall from 55% to 77%. Within all Prognostic groups there are high relative and absolute risk reductions. The distribution of cases to Prognostic groups shows only a small increase in the numbers in better groups. CONCLUSION: The updated survival figures overall and for each Prognostic group for the NPI are presented.