Development and validation of a new predictive model for breast cancer survival in New Zealand and comparison to the Nottingham prognostic index

Mark Elwood, Essa Tawfiq, Sandar Tin Tin, Roger J. Marshall, Tung M. Phung, Ian Campbell, Vernon Harvey and Ross Lawrenson

The only available predictive models for the outcome of breast cancer patients in New Zealand (NZ) are based on data in other countries. We aimed to develop and validate a predictive model using NZ data for this population, and compare its performance to a widely used overseas model, the Nottingham Prognostic Index (NPI).

We developed a model to predict 10-year breast cancer-specific survival, using data collected prospectively in the largest population-based regional breast cancer registry in NZ (Auckland, 9182 patients), and assessed its performance in this data set (internal validation) and in an independent NZ population-based series of 2625 patients in Waikato (external validation). The data included all women with primary invasive breast cancer diagnosed from 1 June 2000 to 30 June 2014, with follow up to death or Dec 31, 2014. We used multivariate Cox proportional hazards regression to assess predictors and to calculate predicted 10-year breast cancer mortality, and therefore survival, probability for each patient. We assessed observed survival by the Kaplan Meier method. We assessed discrimination by the C statistic, and calibration by comparing predicted and observed survival rates for patients in 10 groups ordered by predicted 10-year survival. We compared this NZ model with the Nottingham Prognostic Index (NPI) in this validation data set.

Discrimination was good: C statistics were 0.84 for internal validity and 0.83 for an independent external validity. For calibration, for both internal and external validity the predicted 10-year survival probabilities in all groups of patients, ordered by predicted survival, were within the 95%  confidence intervals (CI) of the observed Kaplan-Meier survival  probabilities. The NZ model showed good discrimination even within the prognostic groups defined by the NPI.

These results for the New Zealand model show good internal and external validity, transportability, and potential clinical value of the model, and its clear superiority over the NPI. Further research is needed to assess other potential predictors, to assess the model’s performance in specific subgroups of patients, and to compare it to other models, which have been developed in other countries and have not yet been tested in NZ.


MonarchE trial



To evaluate whether the combination of abemaciclib (an experimental drug) plus standard endocrine/hormonal therapy improves outcomes in women or men with hormone receptor positive (HR+) & human epidermal receptor 2 negative (HER2 -) high risk breast cancer compared to endocrine therapy alone.

Scientific Title

MonarchE: Protocol I3Y-MC-JPCF A Randomized, Open-Label, Phase 3 Study of Abemaciclib Combined with Standard Adjuvant Endocrine Therapy versus Standard Adjuvant Endocrine Therapy Alone in Patients with High Risk, Node Positive, Early Stage, Hormone Receptor Positive, Human Epidermal Receptor 2 Negative, Breast Cancer


Breast cancer is the most frequently diagnosed cancer among women and is a major cause of cancer-related deaths worldwide. The most prevalent sub-type of breast cancer is hormone receptor-positive (HR positive), human epidermal growth factor receptor 2-negative (HER2 negative) breast cancer and accounts for 70% of all breast cancers.

Approximately 90% of breast cancer patients are diagnosed at an early stage of their disease. With current standard of care hormonal/endocrine therapy and chemotherapy, approximately 30% of HR positive breast cancer patients who are initially diagnosed at early stage, experience distant relapse with metastases (spread of the cancer from the primary site to other parts of the body). Thus, there is a critical need to improve the absolute benefit of adjuvant endocrine therapy for HR positive breast cancer patients who are at high risk of disease recurrence.

Abemaciclib is an oral drug which stops the production of proteins in the body called CDK4 and CDK6, which are responsible for promoting cell growth. This mechanism and abemaciclib has been shown to have antitumour activity and significantly reduce tumour growth, including breast cancer.

This clinical trial is an industry sponsored (Eli Lilly) trial.

Enrolment: Closed

The impact of different tumor subtypes on management and survival of New Zealand women with Stage I-III breast cancer

Ross Lawrenson, Chunhuan Lao, Ian Campbell, Vernon Harvey, Sanjeewa Seneviratne, Mark Elwood, Diana Sarfati, Marion Kuper-Hommel

This study aims to describe the prevalence and characteristics of the different ER/PR/HER2 subtypes in New Zealand women with breast cancer, and to explore their treatment and outcomes.

This study included women diagnosed with Stage I–III breast cancer between January 2006 and May 2013, recorded in the combined Waikato and Auckland Breast Cancer Registers, and with complete data on their ER, PR and HER2 status. Five ER/PR/HER2 phenotypes were classified. Kaplan-Meier method and Cox proportional hazards model were used to examine the survival differences among these subtypes.

Of the 6,875 eligible women, 4,274 (62.2%) were classified as Luminal A, 836 (12.2%) as Luminal B HER2-, 605 (8.8%) as Luminal B HER2+, 401 (5.8%) as HER2+ non-Luminal and 759 (11.0%) as Triple Negative. Maori and Pacific women were less likely to have Triple Negative disease, while Pacific women were more likely to be HER2+ non-Luminal. The five-year breast cancer-specific survival was worst for HER2+ non-Luminal (80.1%) and Triple Negative (81.9%), followed by Luminal B HER2- (89.3%) and Luminal B HER2+ (91.6%), and was the best for Luminal A (96.8%). The adjusted breast cancer-specific mortality hazard ratio for Triple Negative and HER2+ non-Luminal compared to Luminal A was 4.91 (95% CI: .86–6.26) and 3.94 (95% CI: 2.94–5.30), respectively.

The pattern of phenotype in women with Stage I-III breast cancer is  similar to the overseas cohorts. Most New Zealand women with Luminal A breast cancer have a very good prognosis, but the less common subtypes have relatively poor outcomes.



The purpose of this study is to see whether a specialised laboratory test (Prosigna (PAM50) Assay) of breast cancer tissue can be used to choose wāhine / women who can safely avoid radiation therapy because there is a low risk of the cancer coming back.

The EXPERT trial presents a unique opportunity to improve personalised use of radiation therapy in patients with early breast cancer according to their individual risks of local recurrence.

Scientific Title

Protocol ANZ 1601/BIG 16-02: A randomised phase III trial of adjuvant radiation therapy versus observation following breast-conserving surgery and endocrine therapy in patients with molecularly characterised luminal A early breast cancer.


The current standard of care for patients with early breast cancer after breast conserving surgery is hormonal therapy (if HR-positive) and also radiation therapy to the breast to improve local control and survival. However, breast cancer is a complex disease and the benefit of radiation therapy in individual patients varies substantially. Radiation therapy may not be needed for some women with certain types of early breast cancer.

Using the current breast radiotherapy may potentially lead to overtreatment for a proportion of women, and unnecessary treatment toxicity, financial costs and logistical challenges.

If doctors could identify (using the Prosigna PAM50 assay) women who have a very small risk of the cancer coming back, these women may not need radiation therapy and could avoid its side effects.

Enrolment: Open

EXPERT is an international clinical trial, let by Breast Cancer Trials. It will enrol 1170 patients and is open to wāhine / women aged 50 years or older, with Hormone Receptor (HR) positive, Human Epidermal Growth Factor Receptor 2 (HER2) negative, early-stage breast cancer.

Ask your Breast Surgeon or Oncologist if this trial is suitable for you.



In association with the Quality of Life Group (QLG) of the European Organisation for Research into Treatment of Cancer (EORTC), the purpose of this study was to develop a measure, which could be used in the future to investigate the quality of life of women undergoing or having undergone different types of breast reconstruction.

Scientific Title

Phase 4 – An international field study of the Reliability and Validity of an EORTC breast reconstruction questionnaire to assess quality of life in all types of breast reconstruction.


Breast reconstruction has shown important consequences on psychological well-being, quality of life, and the ability to cope with the negative emotional and psychological impact that is associated with a mastectomy. In association with the Quality of Life Group of the European Organisation for Research into Treatment of Cancer (EORTC), Waikato surgeons assisted with the development of a questionnaire to be used in the future to evaluate the quality of life of women undergoing different types and timings of breast reconstruction. This research was coordinated through the University of Bristol, England, and will enroll 360 women from around the world.


This study confirmed the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire as valid for evaluating quality of life and satisfaction after breast reconstruction.


Z.E. Winters et al. International validation of the European Organisation for Research and Treatment of Cancer QLQ-BRECON23 quality-of-life questionnaire for women undergoing breast reconstruction. British Journal of Surgery. Feb, 2018: 105 (3): 209-222.

Lymph Node Grafting


The trial is looking into lymph node grafting for upper limb lymphoedema following breast cancer treatment. With an aim of determining whether lymph node grafting plus standard lymphoedema therapy produces a greater reduction in lymphoedema volume and improved quality of life for those with upper limb lymphoedema.

The trial will compare the novel surgical technique of lymph node grafting in addition to standard lymphoedema therapy against standard lymphoedema therapy alone. Clinical trial participants will be those with residual stage one to two breast-cancer related lymphoedema despite initial treatment with standard lymphoedema therapy and participants are randomised either surgery plus standard therapy or standard therapy alone.

The surgical procedure involves lymph node grafting from groin to upper limb. This technique is carried out by trained Plastic and Breast Surgeons and involves an incision in the groin with removal of two lymph nodes under local anaesthetic. Lymph nodes are then grafted into the subcutaneous tissue of the elbow and wrist of the affected limb. Surgeons have a minimum of five years experience and the surgery is carried out in one surgical procedure and takes approximately 60 minutes.

Scientific Title

Lymph node grafting for upper limb lymphoedema following breast cancer treatment


Upper limb lymphoedema is a common and often distressing side effect of breast cancer treatment. Reconstructive lymphatic microsurgery may be considered if conservative treatment fails but is highly specialized and expensive.


The trial is open to wāhine / women in New Zealand that meet the following criteria:

  • upper limb lymphoedema* of severity stage one (but requiring the regular use of a compression garment) or stage two (ISL staging system)
  • previously treated stage 1-3 breast cancer
  • undergone local standard lymphoedema therapy for at least three months prior to enrolment and continues participation with techniques
  • fit for operative procedure

*definition of lymphoedema being: has either a 200ml interlimb difference or a 10% difference in limb volume.

Note – key exclusion criteria:

  • metastatic breast cancer
  • past history of other malignancy with potential lymphatic drainage to either axillae
  • BMI >40
  • current smoker
  • congestive heart failure
  • low serum albumin (<32g/L)
  • poorly controlled diabetes (HbA1c > 70mm/L)
  • steroid medication


Contact Heather Flay for more information regarding enrolment:


Phone: 07 839 8726 ext 97960




This clinical trial has been made possible by a grant from the Cancer Society of New Zealand, support for surgery from Alison Surgical Centre and Braemar Hospital. Funds raised from the Fine Homes Tour 2017 and the Waikato Sunrise Rotary have also enabled this research. Mr Winston McEwan (Plastic Surgeon and Prinicpal Researcher) and Mr Ian Campbell (Breast Surgeon and Co-Researcher) also donate their time.

Obesity and breast cancer outcomes in chemotherapy patients in New Zealand – a population-based cohort study

Mark Elwood, Sandar Tin Tin, Marion Kuper-Hommel, Ross Lawrenson and Ian Campbell

Obesity has been reported as an adverse prognostic factor in breast cancer, but inconsistently, and under-treatment with chemotherapy may occur. We provide the first assessment of obesity and breast cancer outcomes in a population-based, multi-ethnic cohort of New Zealand patients treated with chemotherapy.

All 3536 women diagnosed with invasive breast cancer in the Waikato region of New Zealand from 2000-2014 were registered and followed until last follow-up in specialist or primary care, death or Dec 2014; median follow-up 4.1 years. For the 1049 patients receiving chemotherapy,  mortality from breast cancer, other causes, and all causes, and rates of loco-regional and of distant recurrence, were assessed by body mass index (BMI), recorded after diagnosis, adjusting for other clinico-pathological and demographic factors by Cox regression.

BMI was known for 98% (n=1049); 33% were overweight (BMI 25-29.9), 21% were obese (BMI 30-34.9), and 14% were very obese (BMI 35+). There were no significant associations between obesity and survival, after adjustment for demographic and clinical factors (hazard ratios, HR, for very obese compared to BMI 21-24, for breast cancer deaths 0.96 (0.56-1.67), and for all deaths 1.03 (0.63-1.67), respectively, and only small non-significant associations for loco-regional or metastatic recurrence rates (HR 1.17 and 1.33 respectively). Subgroup analyses by age, menopausal status, ethnicity, stage, post-surgical radiotherapy, mode of diagnosis, type of surgery, and receptor status, showed no associations. No associations were seen with BMI as a continuous variable. The results in all patients irrespective of treatment but with recorded BMI data (n=2296) showed similar results.

In this population, obesity assessed post-diagnosis had no effect on survival or recurrence, based on 1049 patients with chemotherapy treatment with follow-up up to 14 years.


Ethnic disparities in breast cancer survival in New Zealand: which factors contribute?

Sandar Tin Tin, Mark Elwood, Charis Brown, Diana Sarfati, Ian Campbell, Nina Scott, Reena Ramsaroop, Sanjeewa Seneviratne, Vernon Harvey and Ross Lawrenson

New Zealand has major ethnic disparities in breast cancer survival with Māori (indigenous people) and Pacific women (immigrants or descended from immigrants from Pacific Islands) faring much worse than other ethnic groups. This paper identified underlying factors and assessed their relative contribution to this risk differential.

This study involved all women who were diagnosed with primary invasive  breast cancer in two health regions, covering about 40% of the national population, between January 2000 and June 2014. Māori and Pacific patients were compared with other ethnic groups in terms of demographics, mode of diagnosis, disease factors and treatment factors. Cox regression modelling was performed with stepwise adjustments, and hazards of excess mortality from breast cancer for Māori and Pacific patients were assessed.

Of the 13,657 patients who were included in this analysis, 1281 (9.4%) were Māori, and 897 (6.6%) were Pacific women. Compared to other ethnic groups, they were younger, more likely to reside in deprived neighbourhoods and to have co-morbidities, and less likely to be  diagnosed through screening and with early stage cancer, to be treated in a private care facility, to receive timely cancer treatment, and to receive breast conserving surgery. They had a higher risk of excess mortality from breast cancer (age and year of diagnosis adjusted hazard ratio: 1.76; 95% CI: 1.51–2.04 for Māori and 1.97; 95% CI: 1.67–2.32 for Pacific women), of which 75% and 99% respectively were explained by baseline differences. The most important contributor was late stage at diagnosis. Other contributors included neighbourhood deprivation, mode of diagnosis, type of health care facility where primary cancer treatment was undertaken and type of loco-regional therapy.

Late diagnosis, deprivation and differential access to and quality of cancer care services were the key contributors to ethnic disparities in breast cancer survival in New Zealand. Our findings underscore the need for a greater equity focus along the breast cancer care pathway, with an emphasis on improving access to early diagnosis for Māori and Pacific women.


Study Of Letrozole Extension (SOLE) trial


The SOLE trial aimed to find out if taking letrozole intermittently was better than taking it continuously.

Scientific Title

IBCSG 35-07/BIG 1-07. A phase III trial evaluating the role of continuous letrozole versus intermittent letrozole following 4 to 6 years of prior adjuvant endocrine therapy for postmenopausal women with hormone-receptor-positive, node-positive early-stage breast cancer


Previous research has indicated that breast cancers may be more sensitive to intermittent treatment with letrozole.


SOLE trial results showed that letrozole taken for 9 out of every 12 months, is as good as continuous letrozole in the extended treatment of early-stage breast cancer. No new side effects were noted, beyond what is already known about letrozole. Importantly, women who took intermittent letrozole reported that their quality of life was better, compared with those who took continuous letrozole. This may be because they were able to have time off letrozole, and the side effects were less during that break.

Now, because of this trial, women who have a sufficiently high chance of breast cancer recurrence to require 10 years of hormone-blocking therapy can safely have a break from that treatment for 3 months every year. This strategy may be particularly worthwhile for women who are experiencing troublesome side effects but want to remain on the medication to minimise their chance of breast cancer recurrence.

Main publication

Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial. Marco Colleoni et al on behalf of the SOLE Investigators. Lancet Oncology. 17 November, 2017; S1470-2045(17)30715-5.



The POSNOC trial is a clinical research trial available in NZ looking at the armpit treatment provided to women diagnosed with early stage breast cancer and one or two sentinel nodes involved with cancer spread. The trial will help determine if axillary treatment is no longer needed meaning that some wāhine/women will be able to avoid unnecessary treatment and long term side effects of treatments.

POSNOC is of considerable importance in terms of improving outcomes for women with breast cancer and also in understanding breast biology.

Scientific Title

Protocol RD-5103-001-13: POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy. A randomised controlled trial of axillary treatment in women with early stage breast cancer who have metastases in one or two sentinel nodes or “POSNOC trial”.


The usual treatment following breast cancer surgery is to give chemotherapy or endocrine therapy (hormone therapy), or both. Radiotherapy may also be given to the breast or chest wall. These treatments are called adjuvant therapy.

At the moment, it is also usual for women with cancer spread in 1 or 2  lymph sentinel nodes to have further treatment to their armpit (axilla). This treatment is either an operation to remove extra lymph nodes from the armpit (axillary node clearance), or radiotherapy to the armpit (axillary radiotherapy).  Researchers want to find out whether this further treatment to the armpit is really needed.

Researchers now know that other breast cancer treatments are very good at preventing cancer from coming back. Some research results suggest that the extra armpit treatment after sentinel node biopsy may not change the risk of cancer coming back so the axillary treatment may no longer be needed. However, many experts believe that further evidence is needed to prove whether this is the case.



This UK based trial will involve 1900 women across the UK, Australia, and NZ. Waikato, Rotorua, and Palmerston North Hospitals will be centres for this research.

Ask your Breast Surgeon or Oncologist if this trial is suitable for you.

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