The New NICE Guidelines for Management of Breast Cancer—A Personal Commentary

The new NICE guidelines for management of breast cancer—a personal commentary

Chris Poole, Professor of Medical Oncology, University of Warwick, and Honorary Consultant Medical Oncologist, University Hospital Coventry and Warwickshire NHS Trust

Introduction

The National Institute for Health and Clinical Excellence (NICE), has just issued two more sets of guidelines for oncology specialists, on the management of (i) early-stage and locally advanced, and (ii) advanced breast cancer.^1,2 As with each NICE pronouncement, they call to mind the R word—rationing. In this article, I consider how rationing was seen as a force for good at the beginning of World War II, only to be reviled by the public when it persisted beyond 1945, into peacetime. I look at how doctors embraced rationing for its public health qualities as well as its inherent fairness at a time of shortage and national crisis, but how the profession is now conspicuously unimpressed by the pronouncements of our powerful but distinctly nasty ‘rationing institute’. Finally, I ponder some of the less welcome details embedded in the latest NICE verdict on breast cancer.

The nice face of rationing

Rationing, as we think we understand it, was imposed in World War II to harness the country’s economy to common effective endeavour, which as a by-product promulgated a sense of national unity, and undoubtedly improved the health of the populace. Arguably, much of the electorate’s distaste for food rationing stemmed from its extension 9 years into the peace, after the enemy was beat, but at a time when the nation was burdened by massive debts as well as the immense costs of reconstruction.

Doctors were closely involved with rationing from its inception. Much of the underlying nutritional science had a sound theoretical basis in pre-war work on food composition by Professor Robert McCance and Dr Elsie Widdowson. At the outbreak of the war, they were charged with investigating whether the supply of home-produced food might be stretched by rationing to meet the nutritional needs of the populace. They studied the effects of a diet that some considered intolerable by living on it themselves for 3 months, before finally undertaking a 12-hour, 36-mile hike across the Lake District, including a 7,000 ft climb to prove the diet’s effectiveness in sustaining hard, physical activity.³ The War in the Atlantic aside, from a medical perspective, nearly 7 decades on, wartime food rationing seems to have been an unqualified success: infant mortality declined, and the average age at which people died from natural causes increased. And certainly to me, as an undergraduate, the sight of a lean, fit, sparkly eyed 90-odd-year-old McCance wobbling about on his bike in plus fours was a great advert for a lifetime of black coffee for breakfast, an apple for lunch and plenty of potatoes and sprouts for dinner.

In this edition of Cancer Services Forum, Professor Chris Poole’s personal commentary on the new NICE guidelines for breast cancer provides a colourful account of what he describes as NICE rationing. He discusses some controversial issues around continuing inequalities, a perceived non-transparency of data analysis and the problems with clinical trial crossover when looking for meaningful endpoints on which to base funding decisions.

And now, the NICE face

So, given our general approval, as a profession, for rationing in the 1940s, why do we—and our patients—fail to sense any warm glow of righteous positivity in the aura of healthcare rationing imposed by NICE in 2009?

Well, as oncologists, the only war we’re involved in is the battle against cancer, and what we have sensed over the past few years is, on the one hand, a frustrating series of delays and restrictions in the supply of magic bullets, and on the other, some very strict rules of engagement, masquerading as ‘guidelines’. The latter term is particularly misleading; put simply, clinical activity outside of the so-called guidelines will not be commissioned and, since no organisation with an obligation to balance its books can brook unfunded activity, it will not be permitted. Forget clinical freedom; what with clinical governance, audit, job plan review and appraisal processes in place, and part of our contracts, a subaltern in Helmand probably has greater scope for using his initiative and discretion than a Consultant Medical Oncologist.

Furthermore, unlike rationing in the 1940s, there is no sense of fairness, and absolutely no sense of our all being in it together. Indeed, possession of private medical insurance effectively provides access to a legal ‘black market’ for a section of the population. Thus, many oncologists now practise two standards of medicine—one Neulasta^® injection for the rich, and 10 days of granulocyte colony stimulating factor (G-CSF) injections for the poor, or maybe no prophylactic G-CSF at all, depending on network policy. Lastly, there’s no sense of improved health as an unplanned by-product, instead unwelcome frustration and suffering inherent in disease progression.

The much-trumpeted uniformity of care across the NHS remains a myth. The major impact of NICE on clinical activity has been to delay the introduction of new drugs into the NHS. And, until very recently, the prospect of a patient’s treatment being funded as a special case outside of NICE guidelines depended more on the imagination and literary skills of the consultant than on clinical reality.

Another source of unease for many oncologists is the lack of transparency as to the nature of the criteria on which so many NICE technology assessments are based, in particular, the play of health economic data around the phase III clinical trial endpoints of disease progression, relapse-free survival and overall survival.

There are two particularly widely held concerns. The first centres on the impact of trial crossover on the natural history of malignant disease. For a chronic disease like metastatic breast cancer, progression-free survival provides the cleanest data cut, and many an ethically minded data and safety monitoring committee has authorised the subsequent use of the research intervention in the control arm, thus blurring the evidence for any impact on survival.

The second concern relates to the methodology used to assay the additional costs of a new drug used in combination, and the inevitable failure of any intervention so structured to meet NICE’s criteria on cost per quality adjusted life year (QALY). Both elements of the combination are costed together in the denominator, but only the incremental QALY gain is used in the numerator, making such combinations appear expensive for the benefits gained.

Changing times

Our view of NICE is set to change—clinical guidelines are going to have a more prominent role in our professional lives. When the House of Commons Health Select Committee last appraised NICE in January 2008, it called for the following:⁴

• Greater help for primary care trusts (PCTs) to implement guidance
• Better assessment of the level of uptake of guidance
• A stronger role for PCTs in the development of guidance
• More effective use of experts in the development of guidance
• A change in the terminology used by NICE, to clarify to patients what they can and cannot expect by right from their local NHS organisations
• The recommendation that certain elements of clinical guidelines should be made explicitly mandatory

No doubt these edicts reflect recognition of new militancy in PCT management; as clinicians we have seen PCTs demonstrable willingness to delay the introduction of expensive new treatments, by appealing against NICE recommendations, without reference to their own lead clinician or even their Network Drug and Therapeutics Committee.⁵

NICE—the nastier side

One widespread criticism of NICE has been a perception that it does not afford sufficient weight to the expert knowledge and views of oncologists when it formulates health technology appraisals. A similar deficit is not seen in the composition of committees charged with guideline formulation. However, many of us remain frustrated by the self-confessedly limited scope of so many NICE deliberations.

One example, from the recent NICE guidelines on early breast cancer, is the specific exclusion of the use of paclitaxel in the adjuvant context.¹ At first, many of us presumed this statement reflected restriction of scrutiny to licensed indications. However, the introduction to the document makes clear that a number of recommendations refer to the use of products outside of licence, and stresses the importance of written informed consent in such circumstances. The NICE ruling against paclitaxel is bewildering; it is difficult to attribute it to the clinicians involved or to the guideline review panel, charged as it was with looking after the interests of stakeholders, many of whom might have appreciated access to a generic adjuvant taxane, with different toxicities from docetaxel, a drug which requires the expense and hassle of growth factors for safe administration.

Which brings me to my last general point: by virtue of its timelines, NICE ostensibly seeks to set science in aspic. Evidence drips week by week, opinion changes month by month and professional consensus evolves with the passing of the seasons. By contrast, NICE guidelines change every few years. They are out of date in terms of content or emphasis as soon as they are printed.

So what of the recent NICE guidelines for the management of breast cancer—one set each for early and advanced disease? What are the commissioners going to commission and the auditors going to audit?

Early and locally advanced breast cancer¹

In truth, there is much to endorse in the guidelines, such as the use of aromatase inhibitors for the treatment of women with early-stage, higher-risk, node-positive, ER-positive breast cancer.

Key priorities for implementation

The section of the guidelines on key priorities is tidy and didactic. It also contains evidence-free aspirations—the timelines for starting adjuvant systemic therapy (31 days), and for the annual follow-up mammography interval (12 months). To criticise these points might be seen as to cavil, but both amount to a widespread change in practice, have the potential to render services chaotic, and provide a completely nebulous windmill-tilting audit standard.

MRI investigation

The guidelines are vague about the limitations of MRI as a routine adjunct to the investigation of early breast cancer. After the preliminary results of the COMICE trial⁶ of MRI at San Antonio, 2008, are any of us confident of this modality’s utility, even for defining the extent of lobular carcinoma? It may seem sensible enough to use MRI for dense breasts, and to resolve size discrepancy resulting from other modalities but, again, COMICE has shown us that 28% of MRI-intimated ostensible multi-focal disease was not confirmed pathologically.

Surgery

Then we come to the advice on surgery for early and locally advanced breast cancer, and the blanket assertion that all patients should be recommended sentinel lymph node biopsy (SLNB) as a preliminary surgical approach to the axilla, after permissive routine ultrasound staging. What of the alternative management policy, informed by the use of the Memorial Sloan Kettering (MSK) nomogram, to estimate the likelihood of sentinel lymph node involvement? If the chance of involvement is high, there may be an option to proceed straight to an economical and humane clearance, requiring just one general anaesthetic. Also, what if we choose not to ultrasound the axilla of such patients, on the grounds that we have already decided on clearance? Alternatively, if the sentinel nodes are involved, what if the nomogram predicts that the probability of additional nodal involvement at formal clearance is extremely low? Are we not to discuss this prediction with the patient, to inform her decision as to whether to proceed to clearance? The predictive power of the MSK nomogram has recently been confirmed in an American study⁷ of 3,786 patients and in an audit we have carried out of 200 patients at University Hospital, Birmingham, and it merits further formal UK-based evaluation.

Another inexplicable omission from the surgical guidelines is any attempt to provide formal advice on the optimal resection margins for invasive disease. I think we should be told why not.

Systemic therapy

Regarding systemic therapy, the new NICE guidelines recommend that patients with lymph-node positive early or locally advanced breast cancer should be offered a chemotherapy regimen containing docetaxel. The decision is based in large part on the findings of the BCIRG 001 trial.⁸ This would be most welcome were docetaxel simply endorsed as a valuable and important option for some patients, but why exclude higher-risk, node-negative patients, whose NPI may be similar? And, as I mentioned earlier, the categorical statement that paclitaxel should not be offered, undermines the therapeutic community’s aspiration to practice evidence based medicine; NICE’s reasoning is far from clear and they have made themselves look ridiculous. Furthermore, it will cost the health service.

However, for me, the most radical step in the new guidelines on early and locally advanced disease is the dumping of quantitative measurement of progesterone receptor (PR) expression in routine histological assessment before reaching a decision about adjuvant therapy. This could not be worse timed; not only does it coincide with the development of selective PR modulators (SPRM) for women with advanced breast cancer, but it is undertaken at a time when oncologists are beginning to get to grips with the biological diversity of breast cancer, and are increasingly keen to use tools that predict treatment benefit and prognosis. In particular knowledge of PR has a potentially major impact on the rational use of adjuvant aromatase inhibitors, specifically health economic considerations based on the number needed to treat. Presumably, NICE’s decision on routine quantitative measurement of PR expression is a cow-tow response to the Select Committee’s advice that “more should be done to encourage disinvestment”, and its declaration to the effect that NICE cannot continue to ignore this recommendation.⁴

However, it is only 3 years since the publication of a retrospective clinical analysis of more than 44,000 patients with oestrogen receptor (ER)-positive breast tumours, in which clinical and biological features in a subset of more than 1,700 were analysed by the status of progesterone receptors, as well as human epidermal growth factor receptor (HER)1 and HER2.⁹ The authors found that ER-positive, PR-negative tumours were larger, divided more rapidly and were more likely to have an abnormal number of chromosomes than ER-positive, PR-positive tumours, and they also more often expressed HER1 and over-expressed HER2. Recurrence was higher among tamoxifen-treated women with ER-positive, PR-negative tumours that expressed HER1 or HER2 than among women with ER-positive, PR-positive tumours that expressed these growth factor receptors. The authors concluded that lack of PR expression in ER-positive tumours might be a marker of aberrant growth factor signalling that could contribute to tamoxifen resistance. In an accompanying editorial, Slamon and colleagues argue: “These data could have a profound translational clinical impact on directing therapeutic interventions for patients who have ER-positive tumors but who display a steroid hormone-resistant or -independent phenotype.”¹⁰

Furthermore, knowledge that a tumour is triple negative (immunonegative for ER, PR and HER2) has implications for exploration of family history, referral to medical genetics and the use of biologically targeted therapy. Several ongoing and planned phase III trials endorsed by the National Cancer Research Network (NCRN) are directed at such patients. Furthermore, the evaluation of poly (ADP-ribose) polymerase (PARP) inhibitors in disease of this kind is a subject of pressing scientific interest. Lastly, most oncologists would have a low threshold for the cautious use of hormone replacement therapy in a woman with debilitating menopausal symptoms and a truly triple-negative tumour. Altogether, a sizeable number of patients could benefit from routine PR assay. And if PR assay is unfunded upfront, you can bet there will be all manner of barriers to getting it done in selected cases retrospectively, which will add to the deleterious impact of delayed decision-making.

One further inconsistency in discussions about adjuvant endocrine therapy in the new guidelines concerns drug interactions involving certain selective serotonin reuptake inhibitors (SSRIs), such as paroxetine and fluoxetine, which are frequently prescribed for hot flushes. The efficacy of SSRIs in this indication is mediated by their inhibition of CYP2D6 cytochrome P450, ordinarily responsible for the metabolic activation of tamoxifen. It is envisaged that the use of these SSRIs might impair the effectiveness of tamoxifen, and the guidelines counsel against their use. But why then ignore the phenotypic variation caused by different genetic alleles in the normal population. The AmpliChip CYP450 test is the first genotyping array to allow simultaneous analysis of 33 CYP2D6 alleles.¹¹ Through identification of intermediate metabolisers and poor metabolisers, could this methodology identify a subset of women who might benefit from higher tamoxifen dosing? There is no guidance offered for now, but time and health economists will tell. NICE might have prioritised this research.

Another criticism of the guidelines on early and locally advanced disease relates to the lack of recommendations on the use of neoadjuvant therapy, or any discussion of its role for some patients as a preferable alternative to radical surgery and reconstruction, particularly since so many patients are candidates for adjuvant chemotherapy anyway.

Furthermore, with the recognition that the prospects of pathological complete response are so much higher for triple-negative or HER2-positive patients, there is scope for increasingly rational decision-making. NICE has chosen to ignore specific advice on this issue from stakeholders in the Midlands, who pointed out the critical importance of knowledge of HER2 status when post-operative adjuvant therapy was planned at the multidisciplinary team meeting, and that for this to be feasible, HER2 needed to be assayed on the diagnostic core cut needle biopsy, not the operative specimen. NICE also ignored the observation that unless HER2 is determined at the outset on the core, there would be no scope at all for offering trastuzumab-based neoadjuvant combination chemotherapy, with its inherent 40–50% pathological complete response rate^12-14 and all that this implies for improved rates of breast conservation. What a wasted opportunity! How many women nationwide are having unnecessary mastectomies still on this score?

Follow up

Follow up of women treated for early breast cancer is another area of controversy, and the guidelines suggest that patients might be asked to choose between primary, secondary or shared care. This advice is based on studies from Canada, which showed no detriment to patients followed up in the community—by specially trained team members. The significance of this last point seems to have been missed. If we are to delegate follow up to GPs, they require training.

There is also no mention of rational individualisation of the follow-up plan based on tumour biology. Triple-negative patients rarely relapse more than 3 years out (but of course we won’t identify them without routine PR assay).

Advanced disease²

By and large, the guidelines on management of advanced breast cancer are, in my view, less contentious than their early breast cancer stable mate. They state that systemic disease-modifying chemotherapy should be offered to patients with advanced breast cancer, and the suggested treatments include:

• Docetaxel-based chemotherapy for patients who have already received anthracyclines or where anthracyclines are contraindicated
• Endocrine therapy for ER-positive patients
• Trastuzumab for patients whose tumours over-express HER2

However, there are some areas for concern. The guidelines assert dogmatically that patients whose tumours were HER2-negative at the outset should not be biopsied again at metastatic relapse, even though it is known that approximately 10% of these tumours transform to a phenotype that overexpresses HER2, and may become candidates for trastuzumab.

The guidelines also state that patients with metastatic disease that progress on a trastuzumab and taxane combination should not continue treatment with a second trastuzumab combination, typically vinorelbine-based, in pursuit of synergy, and that trastuzumab should be withdrawn. Although they suggest this topic as an area ripe for further study, the authors fail to take cognisance of the von Minckwitz data,¹² and the lack of residual equipoise about this question in most clinicians’ minds. Lastly, they have neglected to clarify the rational use of non-steroidal and steroidal aromatase inhibitors, and faslodex in this context, another opportunity lost.

Conclusion

The collapse of the worldwide economy and unprecedented government spending in a desperate attempt to maintain the liquidity of the financial system conspire to place the NHS spend under increasingly stringent scrutiny. As a result, we can expect these latest guidelines on breast cancer to be policed rigidly.

Be afraid, be sorely afraid, and if you think I am guilty of sensationalism, I respectfully refer you to the executive summary of the Select Committee Report,⁴ printed in January 2008, at a time when all except Vince Cable were blind to the meteorology of the economic storm on the horizon. It states: “We conclude that NICE does a vital job in difficult circumstances.... Healthcare budgets in England, as in other countries, are limited. Patients cannot expect to receive every possible treatment. Demand outstrips resources and priorities have to be determined. In other words, rationing is essential, and NICE has a key role to play. In the past, NICE has changed in response to new challenges, and we are sure it can do so again. Given the difficult environment, NICE requires the backing of the Government. Ministers must support NICE, not seek to undermine it. NICE must not be left to fight a lone battle to support cost and clinical effectiveness in the NHS.”

We all know what’s happened to the economy in the last 12 months and the impact on government finances. Think about the consequences to the NHS. So the writing is on the wall; this really is the phoney war. It is time to bang the drum, but for the reincarnation of McCance on his bike, rather than Drake and his bowls. Of course, McCance would start with public health and primary care, in which context banning smoking in pubs is pure genius. But while prevention is better than cure, is it really relevant to the alleviation of a short-term crisis? It might be, if we’re talking about a difficult decade. And what if we try to stage shift all common solid tumours, not just breast cancers; after all, we may have now reached the point where investigation may be cheap compared with treatment. Can we then work on that traditional cornerstone of the NHS, the GP gatekeeper, and replace the notion that you do not examine or refer a patient until she’s presented with the same problem three times, by inoculating with the notion that the patient in front of them in surgery today may have cancer? We have done it for breast lumps, almost. Checking out the ramifications of this suggestion might constitute more gainful employ for a health economist than the application of the Markov model of health state utilities analysis to fourth line palliative interventions—the ultimate glass bead game for York academics.

Last, my advice is this. Get your secretary to print off all 315 pages of the unexpurgated edition of the new NICE breast cancer guidelines (that’s both the early and advanced texts) and carry them around in your briefcase until you have read them. Irrespective of the content, it will be great physical exercise, and if you cite them selectively and at opportune moments, your PCT will think you are one of them, and you will know what your registrar is talking about.

To view the NICE Guidelines Development Group’s response to this article, please click here.

To comment on this article, please click here.

References

1. National Institute for Health and Clinical Excellence. Early and locally advanced breast cancer: diagnosis and treatment. London: NICE, 2009.
2. National Institute for Health and Clinical Excellence. Advanced breast cancer: diagnosis and treatment. London: NICE, 2009.
3. Ashwell M. McCance and Widdowson. A scientific partnership of 60 years, 1933–1993. London: British Nutrition Foundation, 1993.
4. House of Commons Health Committee. National Institute for Health and Clinical Excellence. First report of session 2007–08. Available at: http://www.publications.parliament.uk/pa/cm200708/cmselect/cmhealth/27/27.pdf (accessed March 2009).
5. Appeal in respect of the Final Appraisal Determination: Pemetrexed for the treatment of malignant pleural mesothelioma from the Chief Executive of Birmingham East and North PCT. Available at: http://www.nice.org.uk/nicemedia/pdf/MesotheliomaBENPCTAppealReceived.pdf (accessed March 2009).
6. Drew PJ, Harvey I, Hanby A et al. The UK NIHR multicentre randomised COMICE trial of MRI planning for breast conserving treatment for breast cancer. San Antonio Breast Cancer Symposium 2008; Abstract 51.
7. Bevilacqua JLB, Kattan MW, Fey JV, Cody HS, Borgen PI, Van Zee KJ. Doctor, what are my chances of having a positive sentinel node? A validated nomogram for risk estimation. J Clin Oncol 2007; 24: 3670–3679.
8. Martin M, Pienkowski T, Mackey J et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 2005; 352: 2302–2313.
9. Arpino G, Weiss H, Lee AV et al. Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. J Natl Cancer Inst 2005; 97: 1254–1261.
10. Wilson CA, Slamon DJ. Evolving understanding of growth regulation in human breast cancer: interactions of the steroid and peptide growth regulatory pathways. J Natl Cancer Inst 2005; 97: 1238–1239.
11. de Leon J, Susce MT, Murray-Carmichael E. The AmpliChip CYP450 genotyping test: integrating a new clinical tool. Mol Diagn Ther 2006; 10: 135–151.
12. von Minckwitz G, Rezai M, Loibl S et al. Effect of trastuzumab on pathologic complete response rate of neoadjuvant EC-docetaxel treatment in HER2-overexpressing breast cancer: results of the phase III GeparQuattro study. ASCO Breast Cancer Symposium 2008; Abstract 226.
13. Peintinger F, Buzdar AU, Kuerer HM et al. Hormone receptor status and pathological response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab. Ann Oncol 2008; 19: 2020–2025.
14. Arnould L, Arveux P, Couturier J et al. Pathologic complete response to trastuzumab-based neoadjuvant therapy is related to the level of HER-2 amplification. Clin Cancer Res 2007; 13: 6404–6409.

Response from David Miles, Adrian Harnett and Fergus Macbeth, on behalf of the NICE Guidelines Development Group

Professor David Miles, Mount Vernon Cancer Centre, Northwood, Middlesex, Dr Adrian Harnett, Consultant Clinical Oncologist, Norfolk and Norwich University Hospital, Norwich, Fergus Macbeth, Director of the Centre for Clinical Practice, NICE.

Chris Poole’s article makes a good read but is full of misdirected and often ill informed criticism. His account of World War II food rationing is fascinating but not relevant. He implies that it was somehow good and necessary, compared with the malevolent rationing that NICE now imposes on the NHS. But the reality is that we live with limited healthcare resources which need to be used wisely and appropriately (call that ‘rationing’ if you want). A world in which oncologists have unfettered clinical freedom is called Utopia, not the NHS. NICE is there to help make appropriate choices on behalf of all NHS patients.

A few of Professor Poole’s misunderstandings include:

• Guidelines are for guidance. They are not mandatory and do not limit a clinician’s ability to make appropriate and justifiable clinical decisions for individual patients
• NICE has actually approved far more cancer drugs than it has turned down and, through the funding directive, has made millions of pounds available for cancer chemotherapy. When there have been delays, these have often not been because of NICE
• NICE’s processes are transparent. The health economics may be complicated, but that does not mean that the methods are opaque
• The very real problem of crossover in trials is well recognised and understood by NICE
• His criticism of the methods of assessing drug combinations makes no sense. The additional cost of providing the combination compared to the comparator regimen is what is used when constructing the ICER (incremental cost effectiveness ratio)
• The pronouncements of the Commons Health Select Committee are not ‘edicts’ and do not necessarily become policy

When NICE develops guidelines, its remit is to be clear, evidence-based and helpful. It strives to achieve this goal despite a background of widely divergent clinical opinion, which is often subjective, even anecdotal.

The current NICE guidelines for early-stage breast cancer¹ have caused some controversy, in two areas particularly, among those involved in the care of women with the disease, as reflected in the article. Firstly, there is unhappiness with the recommendations about the use of taxanes in early-stage disease:¹

• “Offer docetaxel to patients with lymph node-positive breast cancer as part of an adjuvant chemotherapy regimen"
• "Do not offer paclitaxel as an adjuvant treatment for lymph node-positive breast cancer”

Given the publication of E2100 in the New England Journal of Medicine in April 2008 by Dr Sparano (late in the guidelines’ development), this may seem a little harsh.² However, perusal of the ‘Qualifying Statements’ (written to explain the rational basis for the recommendations) might better inform those with anxieties about the headlines.

In the Qualifying Statement following the recommendation not to advocate paclitaxel in the adjuvant treatment of women with lymph node-positive breast cancer, there is a clear explanation of the reasoning of the Guideline Development Group. The statement explains that NICE reviewed the evidence showing a favourable clinical comparison between weekly paclitaxel and 3-weekly docetaxel. Though inclusion of a generic taxane might be seen as inevitably cost-saving, treatment with weekly paclitaxel would multiply the necessary chemotherapy clinic attendances by three—with important implications for service capacity and costs, as well as patient quality of life. A de novo health economic analysis of 3-weekly paclitaxel was not possible, hence the recommendation.

Much debate has also ensued about the guidance on the use of aromatase inhibitors (AIs) in the adjuvant setting. At a time when luminaries such as Rowan Cheblowski³ and Ian Tannock⁴ present diametrically opposing views on their use, the clinician at the coal-face is left bemused and might appreciate some suggestions. Interestingly, the consensus at the St Gallen conference last month took the same line as the NICE guidelines. The expert panel voted 69% in favour of up-front AIs, 15% for a switch and 15% undecided.

To paraphrase the Good Book, whenever two or more breast oncologists are gathered together, debate shall continue long into the night as to the optimal management of breast cancer. While clinical opinion is vital, particularly since new data become available on a virtually daily basis, the guidance issued seeks to provide clinicians with reasonable recommendations supported by evidence with consideration for their pharmaco-economic consequences.

Perhaps the NICE process ought to be more iterative and responsive to new data and, given the available technology, this might be achievable. In the meantime, despite their inevitable limitations, the guidelines have at least sparked debate in this complex field. A guideline that is not controversial is probably not worth publishing.

References

1. National Institute for Health and Clinical Excellence. Early and locally advanced breast cancer: diagnosis and treatment. London: NICE, 2009.
2. Sparano JA, Wang M, Martino S et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 2008; 358: 1663–1671.
3. Chlebowski RT. Optimizing aromatase inhibitor integration into initial treatment strategies in postmenopausal women with hormone-receptor-positive early breast cancer. Breast Cancer Res Treat 2008; 112: 25–34.
4. Seruga B, Tannock IF. Up-front use of aromatase inhibitors as adjuvant therapy for breast cancer: the emperor has no clothes. J Clin Oncol 2009; 27: 840–842.