In an extensively referenced and incisive article, Prof Gilberto Leung lays out the controversial issue of medical manslaughter.1 In English law, the associated legal offence is termed gross negligence manslaughter (GNM). Doctors can be charged and convicted of this offence when a duty of care is breached, with grossly negligent acts or omissions causing patient death. Prosecution of doctors for GNM is rare but on the rise in the UK, and doctors have expressed concerns about the impact such investigations and prosecutions have on staff morale and health services.2

The law with respect to GNM was clarified in the 1994 Adomako case,3 in which the anaesthetist in charge of a patient during an eye operation failed to notice the disconnection of an oxygen pipe for 6 minutes, and the patient died as a result. The jury in this case was directed to “to consider whether that breach of duty should be characterised as gross negligence and therefore as a crime”. What then constitutes ‘gross’ negligence? The guidance provided by Lord Mackay was that the jury should judge how far the defendant’s conduct departed from the standard of care, and the conduct should be ‘so bad’ as to amount to a criminal act. In her award-winning law reform essay, Katherine Wright4 considered the problem of uncertainty regarding the legal test for gross negligence in some detail. She noted that even prosecutors themselves had difficulty articulating their interpretation of gross negligence, and that a solid prosecution policy for this serious charge is lacking. The decision whether or not to prosecute may not be arbitrary but does seem particularly reliant on the prosecutor’s own moral frame or even gut feelings.4

The field of GNM law appears to be oblivious to the field of patient safety improvement, where ‘blame-free culture’ is the paradigm. Jeremy Hunt, the UK Health Secretary, delivered a passion-filled speech titled “From a blame culture to a learning culture” in his address at the Global Safety Summit in March 2016.5 In the speech, he quoted a 1990 case of ‘a bright 24-year-old medical school graduate’ who started his first job in medicine as a pre-registration house officer, and in his first month of duty, he wrongly injected a highly toxic chemotherapy drug to a patient’s spine. The 16-year-old patient died, and the medical house officer and another colleague were prosecuted for medical manslaughter and given suspended jail sentences. The conviction was eventually overturned by the Court of Appeal.

Hunt4 regretted that “…the real crime was missed: as the legal process rumbled on, exactly the same error was made in another National Health Service (NHS) hospital and another patient died because our system was more interested in blaming than learning”. He went on to say, “The blame culture doesn’t just create fear [among] doctors. It causes heartbreak for patients and their families…” Blocked by fear of blame, defensive health care workers shut grieving families out when unexpected patient death occurs.5 Hunt insisted that a blame-free environment promotes learning and openness and that prosecuting such medical mistakes as criminal offences does not help.5

How do we reconcile the observation that, on the one hand, the UK Health Secretary made such a passionate plea for a non-punitive approach, and on the other hand, that investigations and prosecutions for GNM are on the rise? Is the UK of split mind?

Winding the clock back by two decades may help us see how the pendulum has been swinging between the blame-free paradigm and hard legal sanctions. The story might have begun in the US. In November 1999, the Institute of Medicine (now the US Academy of Medicine) issued a groundbreaking report To Err is Human: Building a Safer Health System.6 With this, the US and the rest of the world embarked on a decade-long pursuit of a patient safety agenda. No-blame or blame-free culture became buzzwords throughout the decade.7 8

The premises of this patient safety movement can be simply stated: first, medical errors are common and cause many patient injuries and even deaths; second, most medical errors are caused by underlying unsafe practices, work processes, and poor systems. This is not to say that human factors are not important, but the common notion of bad physicians being the root cause of bad care appeared unfounded in the vast majority of cases. To build safety systems in health care, it is essential to encourage openness in incident reporting and root cause analysis. Lessons will not be learned if the root causes cannot be discussed openly without fear of retribution.

Perhaps the pendulum swung again in 2010 with the NHS Mid Staffordshire Trust tragedy. ‘Tragedy’ is a euphemism for a fairly large scandal, which revealed hundreds of patients having died needlessly as the result of substandard care and staff failings at two hospitals in Mid Staffordshire between January 2005 and March 2009. A public inquiry led by Robert Francis QC produced the Francis Report,9 in which 290 recommendations for improvement were made.

The Francis report was not enough to weather the political storm. In 2013, the UK Prime Minister commissioned Professor Donald Berwick from the US to study Mid Staffordshire’s various accounts and the recommendations of the Francis report to distil lessons to be learned by the UK Government. Berwick, the co-founder of the Institute of Healthcare Improvement and chair of the National Advisory Council of the Agency for Healthcare Research and Quality, is a fervent champion of health care quality and safety. The Berwick report released in October 2013 indicated a complete systems failure during the Mid Staffordshire Trust tragedy.10 It recommended a broad culture change in the NHS: “The way out is through learning, curiosity, commitment, and empathy rather than anger, fear and blame”.10

Berwick’s non-punitive and encouraging approach was hailed by some as having completely dismissed “the nonsense of criminal sanctions in healthcare”.11 This overlooked the part of the report that called for effective regulations to be strong, focused, and detailed, as well as a recommendation “to build a hierarchy of regulatory responses, including making new criminal sanctions” (Recommendation 10, Section VIII).10 The argument was that existent criminal sanctions (including GNM) are not wide enough in scope, and therefore that the UK Government should introduce new sanctions “in cases where healthcare workers or organisations are unequivocally guilty of willful or reckless neglect or mistreatment of patients”. The Berwick report drew on parallels with existing laws that protect mentally incapacitated and mentally ill people under institutional care.

Authors of the Berwick report were conscious of the apparent contradiction of this recommendation on new criminal sanctions with the celebrative ‘blame free’ learning culture advocated in the rest of the report. The report emphasised that supporting NHS staff and hospitals in learning from errors and holding them criminally accountable are not mutually exclusive approaches. This assertion that we can have the best of both worlds (being blame-free and imposing criminal sanctions as a deterrent at the same time) seems neither self-evident nor evidence-based.

Would criminalising health care professionals for wilful neglect improve patient safety? The UK Government has yet to make a decision on this particular recommendation in the Berwick report. The issue has been debated: one proponent has argued that criminal sanctions have worked in public health law. An example is the success of making seatbelt wearing legally compulsory, which has effectively saved many lives.12 However, the example of seatbelt wearing is a poor one: modern health care is extremely complex, and risk mitigation in medical practice is dissimilar from the single requirement of seatbelt buckling.

Medical manslaughter is a difficult subject, and we should be mindful that protection of doctors is not primarily at stake. Insisting on a totally blame-free culture may be idealistic and can be mistaken for not accepting responsibility when medical harm occurs. Even if we accept that medical errors, including fatal medical incidents, are often caused by a mix of systemic and human factors, doctors and management should be accountable for the parts for which they are responsible. Accordingly, accountability and ‘just culture’ have been proposed.13 14 Prosecution for medical manslaughter may be justified in extreme cases of recklessness and blatant violation of standards of care. The difficulty lies in drawing a line between simple negligence due to fleeting lapses of attention under overworked conditions and gross negligence that is truly reckless. As discussed by Leung,1 gross negligence is not a clearly defined legal concept.1 We need a sustainable health care system that cherishes positive efforts to learn and improve care and is just to the public and fair to professionals. Open discussion is the way forward.

The author has disclosed no conflicts of interest. The author had full access to all data, contributed to the paper, approved the final version for publication, and takes responsibility for its accuracy and integrity.

1. Leung GK. Medical manslaughter in Hong Kong—how, why, and why not. Hong Kong Med J 2018;24:384-90. Crossref

2. Medico-Legal Committee. The British Medical Association. Medical and gross negligence manslaughter. Available from: https://www.bma.org.uk/collective-voice/committees/medico-legal-committee/medical-manslaughter. Accessed 14 May 2018.

3. R v Adomako [1995] 1 AC 171.

4. Wright K. When clinical becomes criminal: reforming medical manslaughter. Law Reform Essay. Bar Council of UK. Available from: https://www.barcouncil.org.uk/media/627460/_35__law_reform_essay.pdf. Accessed 18 May 2018.

5. Hunt J. From a blame culture to a learning culture. Mar 2016. Available from: https://www.gov.uk/government/speeches/from-a-blame-culture-to-a-learning-culture. Accessed 18 May 2018.

6. US Institute of Medicine Committee on Quality of Health Care in America. In: Kohn LT, Corrigan JM, Donaldson MS, editors. To Err is Human: Building a Safer Health System. Washington, US: National Academies Press; 2000.

7. Lilleyman J. A blame-free culture in the NHS: quixotic notion or achievable ambition? Perfusion 2005;20:233. Crossref

8. Elmqvist KO, Rigaudy MT, Vink JP. Creating a no-blame culture through medical education: a UK perspective. J Multidiscip Healthc 2016;9:345-6. Crossref

9. UK Government. Report of the Mid Staffordshire NHS Foundation Trust public inquiry. Feb 2013. Available from: https://www.gov.uk/government/publications/report-of-the-mid-staffordshire-nhs-foundation-trust-public-inquiry. Accessed 13 Mar 2017.

10. Department of Health and Social Care, UK Government. Berwick review into patient safety: recommendations to improve patient safety in the NHS in England. 6 Aug 2013. Available from: https://www.gov.uk/government/publications/berwick-review-into-patient-safety. Accessed 18 May 2018.

11. Berwick report highlights nonsense of criminal sanctions in healthcare. Aug 2013. Available from: https://www.pharmaceutical-journal.com/news-and-analysis/berwick-report-highlights-nonsense-of-criminal-sanctions-in-healthcare/11124155.article. Accessed 21 May 2018.

12. Bibby J, Tomkins C. Would criminalising healthcare professionals for wilful neglect improve patient care? BMJ 2014;348:g133. Crossref

13. Walton M. Creating a “no blame” culture: have we got the balance right? BMJ 2004;13:163-4. CrossRef

14. Wachter RM, Pronovost PJ. Balancing “no blame” with accountability in patient safety. N Engl J Med 2009;361:1401-6. Crossref

In a recent article by the Cancer Expert Working Group on Cancer Prevention and Screening,1 screening for breast cancer in the general female population was not recommended based on the lack of evidence for its survival benefit and the imminent cause of patient anxiety. The criticisms of implementing a population-based screening programme for breast cancer include overexposure to radiation and increment in the number of invasive investigations and treatments for breast lesions that may never become malignant. Nonetheless it is important to recognise that the primary aim of screening in breast cancer is to facilitate timely detection of early-stage disease, and hence improve survival. In contrast to this notion, several large-scale studies using nationwide data showed that screening could only prevent one to two cancer deaths in every one to 2000 women screened at the expense of 20% overdiagnosis rates as well as induction of anxiety in every one to 2000 women.2 3 Nonetheless a more in-depth analysis would reveal major weaknesses in these studies including their methodology, inclusion criteria for screening, level of expertise in the evaluation of screening results, and the standard of equipment used for screening. For instance, the Canadian National Breast Screening Study was the only randomised controlled trial that did not show any survival benefit for screening, but a 35% increment in the overdiagnosis of ductal carcinoma in situ.4 Nonetheless randomisations were not blinded and with pitfalls. Women with symptomatic palpable breast masses were also recruited into the ‘screening’ arm, and the quality of mammography was suboptimal and evaluation of mammographic images deficient.

On the contrary, many studies have shown that treatment for smaller tumours without nodal involvement confers better oncological outcomes as well as a better chance of undergoing breast conserving surgery, and fewer postoperative morbidities.5 6 7 This is an important issue that was often not addressed by these large-scale population studies such as the Swiss Medical Board study and the Cochrane review.2 3 The primary end-point of these studies was reduced mortality. They paid no regard to the short-term physical and psychological impact of cancer treatment. The current trend in treatment for breast cancer is multifaceted. A smaller tumour size increases the chances of breast conserving surgery with consequently less postoperative morbidity compared with standard mastectomy.8 Applying the same principle, the advent of sentinel lymph node mapping in the management of the axillary area implied a substantially reduced need for axillary dissection in early tumours, and hence lower risk of lymphoedema and its associated morbidities.9 10 Moreover, advances in imaging techniques may further improve the accuracy of screening. In the Norwegian nationwide study of over 40 000 women with breast cancer, screening led to a reduction in mortality by 4.8 deaths per 100 000 person-years when compared with the non-screened group.11 Furthermore, screening in the ‘modern’ era further reduced mortality by 7.2 deaths per 100 000 person-years compared with screening in the ‘historical’ era implying that changes to breast cancer awareness, advances in imaging techniques, and improved treatments in recent years could all contribute to the survival benefit of a screening programme. Such finding was also in line with the evidence provided by the National Health Service Screening Programme in which there was a steady decline in mortality for women with breast cancer aged between 50 and 79 years as the screening programme evolved over a 10-year period from 1990 to 2000.12 In Hong Kong, there has been a steady increment in the number of new cases of breast cancer over the last three decades. According to the Hong Kong Cancer Registry, breast cancer is now the most common female cancer with over 3500 new cases diagnosed annually.13 Public awareness of breast cancer has substantially improved in recent years following promotion by local media and other non-profitable organisations such as the Hong Kong Breast Cancer Foundation, Well Women Clinic of the Tung Wah Group of Hospitals, and the Family Planning Association. In fact, breast screening in our local population has been shown to be feasible and well accepted.14 Advanced imaging technology such as three-dimensional mammography has been introduced as an alternative efficient assessment tool for screening as well as multidisciplinary management of breast cancer in clinical practice. It may be premature to conclude that screening for the general female population in Hong Kong is of little clinical value.

The author has no conflicts of interest to disclose.

1. Cancer Expert Working Group on Cancer Prevention and Screening. Recommendations on prevention and screening for breast cancer in Hong Kong. Hong Kong Med J 2018;24:298-306. Crossref

2. Gøtzsche PC, Jørgensen KJ. Screening for breast cancer with mammography. Cochrane Database Syst Rev 2013;(6):CD001877. Crossref

3. Biller-Andorno N, Jüni P. Abolishing mammography screening programs? A view from the Swiss Medical Board. N Engl J Med 2014;370:1965-7. Crossref

4. Miller AB, Baines CJ, To T, Wall C. Canadian National Breast Screening Study: 2. Breast cancer detection and death rates among women aged 50 to 59 years. CMAJ 1992;147:1477-88.

5. Cossetti RJ, Tyldesley SK, Speers CH, Zheng Y, Gelmon KA. Comparison of breast cancer recurrence and outcome patterns between patients treated from 1986 to 1992 and from 2004 to 2008. J Clin Oncol 2015;33:65-73. Crossref

6. Metzger-Filho O, Sun Z, Viale G, et al. Patterns of recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international breast cancer study group trials VIII and IX. J Clin Oncol 2013;31:3083-90. Crossref

7. Jacobson JA, Danforth DN, Cowan KH, et al. Ten-year results of a comparison of conservation with mastectomy in the treatment of stage I and II breast cancer. N Engl J Med 1995;332:907-11. Crossref

8. Eby PR. Evidence to support screening women annually. Radiol Clin North Am 2017;55:441-56.

9. Veronesi U, Paganelli G, Viale G, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 2003;349:546-53. Crossref

10. Bromham N, Schmidt-Hansen M, Astin M, Hasler E, Reed MW. Axillary treatment for operable primary breast cancer. Cochrane Database Syst Rev 2017;(1):CD004561. Crossref

11. Kalager M, Zelen M, Langmark F, Adami HO. Effect of screening mammography on breast-cancer mortality in Norway. N Engl J Med 2010;363:1203-10. Crossref

12. Blanks RG, Moss SM, McGahan CE, Quinn MJ, Babb PJ. Effect of NHS breast screening programme on mortality from breast cancer in England and Wales, 1990-8: comparison of observed with predicted mortality. BMJ 2000;321:665-9. Crossref

13. Hong Kong Cancer Registry. Available from: http://www3.ha.org.hk/cancereg/. Accessed Jun 2018.

14. Kwong A, Cheung PS, Wong AY, et al. The acceptance and feasibility of breast cancer screening in the East. Breast 2008;17:42-50. Crossref

Breast cancer is an important health hazard in Hong Kong women. It has been the number one cancer to affect women in Hong Kong for two decades and the number of new cases diagnosed each year is increasing.1 Today, one in 16 women will have breast cancer in their lifetime.1 The local pattern of breast cancer is similar to that in the West, suggesting that a westernised lifestyle and diet may be the underlying driving force.

Owing to advances in a multidisciplinary approach to treatment, breast cancer is no longer solely a surgical disease. An understanding of the tumour biology has led to the development of targeted medical therapy and hence improved outcome for breast cancer treatment. Less radical surgery in appropriate patients and new techniques in radiotherapy have reduced treatment morbidity and improved quality of life for breast cancer survivors.

Breast cancer is a heterogeneous disease. An understanding of the tumour biology has been made possible from gene expression array analysis, leading to the identification of different intrinsic subtypes that exhibit different tumour behaviour with different prognoses, and that may require specific targeted therapies to maximise treatment effectiveness.2 The assay of hormone receptor (oestrogen/progesterone receptor)–related genes, human epidermal growth factor receptor 2 (HER2)–related genes, basal-like genes, and proliferation genes has led to the distinction of at least five intrinsic subtypes, namely luminal A and B, HER2-overexpressed, basal-like, and claudin-low, with the latter two being grouped as triple-negative subtypes. Clinical assays using immunohistochemistry measure surrogates that are used to differentiate the different biological subtypes and guide treatment.

Approximately 20% to 25% of all breast cancers exhibit HER2 overexpression. The development of the first anti-HER2–targeted therapy with trastuzumab more than 15 years ago has significantly improved the survival of breast cancer patients in both neoadjuvant, adjuvant, and metastatic settings.3 Newer agents such as lapatinib, pertuzumab, and an antibody-drug conjugate trastuzumab emtansine (T-DM1), have shown prolongation of disease-free survival.4 Dual blockade using trastuzumab and pertuzumab has shown prolonged survival in patients with advanced HER2-positive cancer when compared with trastuzumab alone.5 Different clinical studies have also confirmed the value of T-DM1 as second- or third-line therapy for advanced breast cancer.6 The paper by Yeo et al7 in this issue reports the results of a multicentre retrospective study of the use of T-DM1 in advanced HER2-positive breast cancer in Hong Kong. It showed that T-DM1 was well tolerated and, despite heavy pretreatment with anti-HER2 agents and cytotoxic chemotherapy, a meaningful achievement of progression-free survival of 6 months was achieved.

Neratinib, a tyrosine kinase inhibitor, given after trastuzumab has been shown to reduce the risk of recurrence or death when compared with placebo, leading to a promising future for advanced HER2-positive breast cancer.8

Approximately 75% of breast cancers express hormone receptors for oestrogen and progesterone. Tamoxifen, a selective oestrogen receptor modulator, was the first targeted therapy and has been used for more than 30 years to treat these hormone receptor–positive breast cancers.9 Recent treatment options have expanded to include agents such as aromatase inhibitors that reduce oestrogen synthesis, and selective oestrogen down-regulators such as fulvestrant. The use of these new agents has improved disease-free and overall survival.

Extended use of endocrine therapy using 10 years of tamoxifen10 or 5 years of tamoxifen followed by 5 years of aromatase inhibitors11 has been reported to reduce recurrence and mortality. For breast cancer with high risk of recurrence, continuation of endocrine therapy beyond 5 years should be considered, provided the side-effects of treatment are tolerable.

Some 20% to 30% of hormone-sensitive breast cancers may develop resistance with consequent recurrence or metastasis. Newer agents such as mTOR inhibitors, or CDK4/6 inhibitors, which target the altered pathways that produce endocrine resistance, have shown promising results when used in combination with anti-oestrogen agents.12 13

Early-stage luminal cancers that are responsive to endocrine therapy may not require adjuvant chemotherapy. Genomic profile assays—such as the 21-gene assay (Oncotype DX; Genomic Health, Redwood City [CA], United States [US]), 70-gene assay (MammaPrint; Agendia, Amsterdam, Netherlands), PAM50 (Prosigna; NanoString Technologies Inc, Seattle [WA], US), and EndoPredict (Myriad Genetics Inc, Salt Lake City [UT], US)—provide additional genomic information about the breast cancer, either by estimating the prognosis or predicting the additional benefit of chemotherapy in early-stage breast cancers.14 15 Studies using some of these assays have shown a reduced need for chemotherapy in about one third of patients who may otherwise be referred for chemotherapy on the basis of clinical and pathological parameters alone.

The promising results of immunotherapy in treating non–small-cell lung cancer and other cancers have led to clinical trials in breast cancer. An improved clinical activity has been observed in treating triple-negative breast cancer and those expressing PD-L1.16 We await further results of clinical trials using immunotherapy.

Regular breast screening introduced in the 1970s has allowed detection of early breast cancer that may not require total mastectomy or complete axillary dissection, thereby reducing long-term morbidity. Long-term follow-up in studies started in the 1980s showed that breast-conserving surgery coupled with radiation has an equivalent outcome to total mastectomy in terms of survival.17 Today, one third of patients can receive breast-conserving treatment, which reduces the psychosocial impact of breast cancer on long-term survivorship.

The development of sentinel node biopsy in the mid-1990s has led to its use in clinically node-negative tumours, thereby reducing the occurrence of lymphoedema that can cause long-term complications in breast cancer survivors.18

The randomised ACOSOG Z11 trial19 that compared sentinel node biopsy alone versus the addition of complete axillary dissection for sentinel node-positive patients has shown no difference in survival outcomes, leading to the recommendation that axillary dissection is no longer valid in patients who undergo breast-conserving treatment and postoperative systemic therapy. This approach has become increasingly adopted in many medical centres despite the criticism of under-recruitment of study cases.

For patients who still require total mastectomy for multicentric early disease, total skin-sparing mastectomy with preservation of the nipple areolar complex has shown no difference in local recurrence. It allows immediate breast reconstruction and maximises the aesthetic outcome of treatment.20 It has therefore gained increasing acceptance in treating carefully selected patients.

Short-course radiotherapy using hypofractionation has been found to result in a similar outcome to standard radiotherapy in terms of local recurrence and survival, without increasing long-term toxicities.21 It is therefore now accepted as a standard of care for early-stage breast cancer.

Whole-breast radiation following breast-conserving surgery aims to create a uniform dose distribution to target tissues with minimal toxicity to normal tissue. Clinical assessment and computed tomography–based treatment planning, together with techniques using compensators such as wedges, forward planning using segments, intensity-modulated radiotherapy, respiratory gating, or prone positioning, have all helped to achieve an optimal outcome.

Post-mastectomy radiotherapy is conventionally given to patients with involvement of four or more nodes to reduce locoregional failure and breast cancer mortality. For patients with one to three nodes, factors such as adverse tumour biology or tumour size of more than 5 cm may shift the decision to recommend radiotherapy after considering the benefits and toxicities.22

An improved understanding of the tumour biology of breast cancer has led to the identification of different intrinsic subtypes. Breast cancer care is now tailored to use the appropriate therapy to target the tumour characteristics of individual cancers, to achieve an improved survival outcome for breast cancer patients. Targeted cancer treatment is proliferating. More scientific work is required to further our understanding of the unknown subtypes, especially in triple-negative cancers, and elucidate the mechanisms that underlie the development of tumour resistance to drug therapy.

The author has disclosed no conflicts of interest.

1. Crude incidence rate of breast cancer in Hong Kong. Available from: https://www.hkbcf.org/article.php?aid=138&cid=6&lang=eng. Accessed 10 Jan 2018.

2. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012;490:61-70. Crossref

3. Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2–positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 2014;32:3744-52. Crossref

4. Swain SM, Baselga J, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 2015;372:724-34. Crossref

5. Patel TA, Dave B, Rodriguez AA, Chang JC, Perez EA, Colon-Otero G. Dual HER2 blockade: preclinical and clinical data. Breast Cancer Res 2014;16:419. Crossref

6. Krop IE, Kim SB, González-Martín A, et al. Trastuzumab emtansine versus treatment of physician’s choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol 2014;15:689-99.

7. Yeo W, Luk MY, Soong IS, et al. Efficacy and tolerability of trastuzumab emtansine in advanced human epidermal growth factor receptor 2–positive breast cancer. Hong Kong Med J 2018;24:56-62. Crossref

8. Chan A, Delaloge S, Holmes FA, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2016;17:367-77. Crossref

9. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Davies C, Godwin J, Gray R, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011;378:771-84. Crossref

10. Davies C, Pan H, Godwin J, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 2013;381:805-16. Crossref

11. Goss PE, Ingle JN, Pritchard KI, et al. Extending aromatase-inhibitor adjuvant therapy to 10 years. N Engl J Med 2016;375:209-19. Crossref

12. Piccart M, Hortobagyi GN, Campone M, et al. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2. Ann Oncol 2014;25:2357-62. Crossref

13. Finn RS, Crown JP, Lang I, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 2015;16:25-35. Crossref

14. Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor–positive breast cancer. J Clin Oncol 2006;24:3726-34. Crossref

15. Harris LN, Ismaila N, McShane LM, et al. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2016;34:1134-50. Crossref

16. Rugo HS, Delord JP, Im SA, et al. Preliminary efficacy and safety of pembrolizumab (MK-3475) in patients with PD-L1-positive estrogen receptor-positive/HER2-negative advanced breast cancer enrolled in KEYNOTE-028 [abstract S5-07]. Proceedings of the San Antonio Breast Cancer Symposium; 2015 Dec 11.

17. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002;347:1227-32. Crossref

18. Krag DN, Anderson SJ, Julian TB, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncology 2010;11:927-33. Crossref

19. Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA 2011;305:569-75. Crossref

20. Piper M, Peled AW, Foster RD, Moore DH, Esserman LJ. Total skin-sparing mastectomy: a systematic review of oncologic outcomes and postoperative complications. Ann Plast Surg 2013;70:435-7. Crossref

21. Whelan TJ, Pignol JP, Levine MN, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med 2010;362:513-20. Crossref

22. Recht A, Comen EA, Fine RE, et al. Postmastectomy radiotherapy: an American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology focused Guideline Update. Pract Radiat Oncol 2016;6:e219-34. Crossref

Trauma and acute stroke services share common features of being time-dependent, high-stakes, resource-intensive, and multidisciplinary in nature; both call for a robust system of care. In Hong Kong, we established a trauma system some one and a half decades ago.1 There is no reason why we cannot and should not do the same for stroke if Hong Kong, for all its worth, is to proclaim itself a ‘world-class city’. We need to build a stroke system.

The fact that stroke will impose a considerable burden on our ageing population needs no elaboration.2 The introduction of intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) has provided us with reliable tools to address these challenges—both IVT and MT are proven and clinically accessible treatments that can significantly improve patient outcomes.3 But while IVT is, arguably, fairly well established in Hong Kong, the provision of MT, as demonstrated by Tsang et al4 in this issue, remains uncoordinated, patchy, and inconsistent.

Mechanical thrombectomy involves the use of endovascular intervention within 6 hours of symptom onset. Its provision can be realised only if patients are directly admitted or secondarily transferred to a specialist unit in a timely manner.3 Although we have the expertise, it is presently spread across too many hospitals, few of which can individually sustain a full-fledged 24/7 stroke service. There is currently no designated stroke centre or sufficiently formalised referral network to ensure that patients will be treated at the right place and at the right time. Far too many patients are being denied these life-redefining therapies. Something needs to be done.

Merely having a few strategically placed stroke centres will not suffice. The singular solution is to adopt a territory-wide ‘system approach’ whereby prehospital diversion, secondary transferral arrangements, protocol-driven triage, and expeditious intervention can become the norm, as it is for trauma.5 Optimal stroke care also encompasses prevention, public education, rehabilitation, post-discharge social care, professional training, audit, and research.6 The presence of a formalised stroke system will serve to raise awareness, lend legitimacy, facilitate cultural change, and entice the injection and consolidation of resources for these purposes. Without it, we will forever sit passively at the receiving end of an impending stroke tsunami, shouting complaints and drowning in our own complacency.

Scientific evidence and judicial outcomes suggest that IVT and MT will likely become not only medically accepted but also legally required standards of care under common law, and a failure to provide these treatments may well fulfil the burden of proof in medical negligence.7 Numerous IVT-related claims have already materialised overseas including, but not limited to, 46 in the United States by 2013.8 The majority of reported cases involved doctors’ failure to treat, and hospitals were often found vicariously liable. In Australia, an inquest is currently underway into the deaths of two stroke patients at a hospital where both stroke interventionists were allowed to go on leave at the same time.9

It takes little imagination to contemplate the first related claim in Hong Kong should our situation remain unchanged. To defend it by saying that ‘we do not yet have these services’ would be untruthful because we do; they are just not properly organised. At present, depending on where one lives or develops a stroke, acute stroke care may be available all the time, during office hours only, or not at all. Although it is unrealistic to expect a comprehensive stroke service at every hospital, doctors can and do have the professional duty to refer. Few of us would question nowadays whether burn or head-injured patients should be transferred to a specialist unit. Stroke patients should be no exception. The question is about knowing where, when, and how.

Stroke claims are invariably expensive and demoralising. From a utilitarian standpoint, we only need a few successful claims to undermine any ‘savings’ gained through inaction, while damage to individual reputations and payouts through indemnity coverage will eventually be transferred to the rest of the professional community. Taxpayers will also want to see their money better spent. We must invest to save.

During the regionalisation of trauma services in Hong Kong, recommendations by external experts were accorded substantial weight and influence. We had unequivocal mandates from the highest authorities within the public sector that provided clear instructions and directions for change. A case-volume–orientated approach superseded the rigid, if not frigid, cluster-based thinking; five instead of seven trauma centres were designated in 2003. Collaboration with the ambulance services soon led to primary trauma diversion whereby patients are sent to the most appropriate centre instead of the nearest hospital. A clear sense of corporate responsibility and ownership was palpable. As a result, we now have a trauma system that is at least accountable if not respectable. Why don’t we take advantage of these valuable experiences and attempt the same for stroke?

The situation for stroke is that professional groups are still expected to work things out among themselves, find solutions, bid for resources, and, should they fail, keep trying. Although this may well be administratively necessary or even sound, more decisive and incisive steering and driving will undoubtedly move things farther and quicker. In the United Kingdom, acute stroke services were regionalised in two metropolitan cities using different strategies. Better access to care was soon established in London, where a top-down approach was used, than in Greater Manchester that adopted a more bottom-up method. Clinical and cost outcomes were correspondingly different.10 The choice and decision is one for the wise. Meanwhile, what we need is a clearer and stronger declaration of the vision and mission to build another respectable and accountable system of care here in Hong Kong.

This is not to say that we should simply copy and paste. What works in other countries may not be applicable here. We must learn, adapt, and be pragmatic. Local lessons from trauma system implementation also taught us that perpetual reliance on good will alone would not sustain something as demanding as a trauma or stroke system; additional resources must be planned for and availed. The designation of a specialist centre is essentially an irremediable step of franchising that has to be done boldly and carefully, as subsequent de-designation can be a potential cause of stroke for some. (We ended up with more trauma centres than we need with no realistic prospect of rectification.) Plainly, we do not want a 90-minute prehospital time for stroke but neither do we need a stroke centre at every street corner. It is a delicate balance between access to care, the concentration of clinical experience, and cost-effectiveness. Similarly, the failure to establish a regional trauma registry was a monumental error that must not be repeated.11 It all comes down to having the will and power to evolve, a lot of common sense, and, of course, proportional and handsome funding.

Hong Kong is blessed with an abundance of medical talent as well as an efficient and arguably well-subsidised health care system. We do not need to re-invent the wheel or try to build Rome. We already have the experience and machinery for change. The needs are real, the liabilities foreseeable, and the responsibilities non-delegable. Instead of leaving our stroke patients to nature’s course, there is much that we can and must do. The people of Hong Kong deserve better. Hong Kong deserves a stroke system.

The author has disclosed no conflicts of interest.

1. Leung GK, Chang A, Cheung FC, et al. The first 5 years since trauma center designation in the Hong Kong Special Administrative Region, People’s Republic of China. J Trauma 2011;70:1128-33. Crossref

2. Woo J, Ho SC, Goggins W, Chau PH, Lo SV. Stroke incidence and mortality trends in Hong Kong: implications for public health education efforts and health resource utilisation. Hong Kong Med J 2014;20(Suppl 3):S24-9.

3. Miller JB, Merck LH, Wira CR, et al. The advanced reperfusion era: implications for emergency systems of ischemic stroke care. Ann Emerg Med 2017;69:192-201.

4. Tsang AC, Yeung RW, Tse MM, Lee R, Lui WM. Emergency thrombectomy for acute ischaemic stroke: current evidence, international guidelines and local clinical practice. Hong Kong Med J 2018;24:73-80. Crossref

5. Whelan KR, Hamilton J, Peeling L, Graham B, Hunter G, Kelly ME. Importance of developing stroke systems of care to improve access to endovascular therapies. World Neurosurg 2016;88:678-80. Crossref

6. Lindsay P, Furie KL, Davis SM, Donnan GA, Norrving B. World Stroke Organization global stroke services guidelines and action plan. Int J Stroke 2014;9 Suppl A100:4-13.

7. Blyth CO, Dudley N. Litigation risks with the National Stroke Strategy. BMJ 2007;335 [Response to: Short R. UK government to spend £105m to improve stroke services. BMJ 2007;335:1231.] Available from: http://www.bmj.com/ content/335/7632/1231.2/rapid-responses. Accessed 26 Nov 2017.

8. Bhatt A, Safdar A, Chaudhari D, et al. Medicolegal considerations with intravenous tissue plasminogen activator in stroke: a systematic review. Stroke Res Treat 2013;2013:562564. Crossref

9. Crouch B. Royal Adelaide Hospital knew its stroke service was ‘indefensible’ time bomb but failed to address it before two patients died. The Advertiser 2017 June 16. Available from: http://www.adelaidenow.com.au/news/south-australia/royal-adelaide-hospital-knew-its-stroke-service-was-indefensible-time-bomb-but-failed-to-address-it-before-two-patients-died/news-story/e0ecfeb7c359347fe461c8caaeca9bf6. Accessed 20 Dec 2017.

10. Fulop NJ, Ramsay AI, Perry C, et al. Explaining outcomes in major system change: a qualitative study of implementing centralised acute stroke services in two large metropolitan regions in England. Implement Sci 2016;11:80. Crossref

11. Leung GK. Trauma system in Hong Kong. Surg Pract 2010;14:38-43. Crossref

Treatment outcomes for patients with cancer have improved greatly, in part due to more aggressive forms of systemic treatments. Such treatments, however, can compromise fertility and this has precipitated a growing focus on fertility issues within the oncology community. International guidelines on fertility preservation in cancer patients recommend that physicians discuss, as early as possible, with all patients of reproductive age their risk of infertility from the disease and/or treatment and their interest in having children after cancer, and help with informed decisions about fertility preservation.1 2 A local study performed in a major teaching hospital reported that up to 32% of male cancer patients encountered deterioration of semen parameters after gonadotoxic treatments.3 The thought of the possibility or actual prior experience of treatment-related infertility can lead to psychological stress.4 5 Patients prefer maintaining their fertility and future reproductive function at the time of cancer diagnosis.6 Fertility concerns may also affect the decision to pursue treatment.7 8 9 As recommended by the American Society of Clinical Oncology2 and the European Society for Medical Oncology,1 sperm cryopreservation and embryo/oocyte cryopreservation are standard strategies for fertility preservation in male and female patients, respectively. Other strategies, which include pharmacological protection of the gonads and gonadal tissue cryopreservation, are currently considered experimental. Whilst these guidelines and recommendations are readily accessible, the ‘bottom-line’ of whether a suitable patient is referred for fertility preservation is entirely dependent on the treating physicians’ awareness and understanding as well as the local availability of fertility-preservation techniques.

In the article that accompanies this editorial, Chung et al10 present the results of a cross-sectional paper-based survey that assessed the awareness of, attitude towards, and knowledge about fertility preservation among 167 clinicians of various clinical specialties in Hong Kong. Specialists in General Surgery, Paediatrics, Clinical and Medical Oncology, and Haematology and Haematological Oncology were included. This is the first such study ever reported from the territory. Obstetrics and Gynaecology (O&G) specialists were also included in the survey and accounted for the largest proportion of respondents by specialty (40.7%). A limitation of this study, however, was that all respondents were specialists working in the public sector, as the communications directory of the Hospital Authority was used to identify potential subjects. The prior referral experiences of the respondents might be different to all O&G specialists in our locality, as there is currently no publicly funded fertility centre in Hong Kong.

Results of this study10 were surprising, to say the least. Without going into the specifics of different types of fertility preservation and their respective indications, less than half of the respondents (45.6%) reported being ‘aware of fertility preservation’. Specialists in O&G fared no better in this regard with only half (50.7%) of the respondents reporting themselves as being aware. As expected, O&G specialists were more aware of fertility-preservation techniques in females such as oocyte- and embryo-freezing as well as ovarian tissue freezing, than their non-O&G counterparts. Interestingly, when respondents were further asked about individual fertility-preservation procedures, an increased awareness was found. In fact, a higher percentage of the same O&G specialists in this study reported to be familiar with “all of the above” fertility-preservation techniques previously itemised, compared with being ‘aware of’ fertility preservation per se (63.6% vs 50.7%). These findings highlight a possible diversity of understanding within our medical community of what constitutes fertility preservation. Moreover, even if knowledge is indeed improved, suitable patients may still not be able to receive appropriate counselling and care, as only a little more than half (55%) of all respondents were aware that there are dedicated clinics and specialists who would be willing to accept referrals for fertility preservation. On a more encouraging note, an overwhelming majority of respondents (97%) felt that at least a dedicated clinic or fertility preservation centre is necessary in Hong Kong, and over half felt at least two centres are required to cater for both private and public patients. This study highlighted a gap in understanding among the medical community and a lack of currently available resources for fertility preservation that must be overcome if we are to truly provide this service effectively.

In general, risks of treatment-related infertility have been described previously by various groups. A recently published modified consensus4 11 divided systemic anti-cancer therapies and radiation therapy of specific doses to gonadal sites into five different risk categories, namely: (i) high risk, corresponding to >80% risk of permanent amenorrhoea in women and prolonged azoospermia in men; (ii) intermediate risk (40%-60% risk of permanent amenorrhoea in women and likelihood of azoospermia in men when given with other sterilising agents); (iii) low risk (<20% risk of permanent amenorrhoea in women and only temporary reduction in sperm counts in men); (iv) very low or no risk of permanent amenorrhoea in women and temporary reduction in sperm count in men; and (v) unknown risk of permanent amenorrhoea in women and effect on sperm production in men. It is important to note that the gonadotoxic effects of newer targeted therapies such as tyrosine-kinase inhibitors and monoclonal antibodies have not been studied in detail. The impact of these agents on a patient’s subsequent fertility has also not been well described. Whilst data are now gradually emerging, there is a need for the oncology community to study the impact of these newer agents on fertility, especially since they have now become the cornerstone of effective anti-cancer treatment. A possible approach may be to analyse large population-based health and cancer registries, and cross-reference individuals who may have received these agents with subsequent successful child-bearing or birth, either through natural or assisted means.

Moving forward, from a societal perspective, it is impractical to educate all clinicians of various specialties about the latest advancements and techniques of fertility preservation. This is also not necessary. What may be a more reasonable approach is for physicians, especially oncologists and haematologists who administer gonadotoxic chemotherapies, to become more diligent in recognising the fertility-preservation needs and concerns of ‘younger’ oncology patients, and to have ready access to referrals and consultative services that fertility specialists can provide. Fertility specialists should also be made more aware of both the improved treatment outcomes as well as their potential toxicities. This should not only be limited to toxicities associated with fertility, but with other physical side-effects as well as potential socio-economic burdens that newer anti-cancer treatments entail.

Physical, psychosocial, and economic impacts of cancer care, as well as the natural history of the disease, will likely affect a patient’s decision about whether to pursue fertility preservation. Younger patients who are often in the prime of their life when struck with the devastating diagnosis of cancer may have different priorities to older adults. The establishment of a dedicated multidisciplinary adolescent and young adults oncology team that consists of physicians and allied health professionals with training and experience in addressing the needs of this unique set of patients, and incorporating fertility preservation as one of its pillars, is the way forward.

1. Peccatori FA, Azim HA Jr, Orecchia R, et al. Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013;24 Suppl 6:vi160-70. Crossref

2. Loren AW, Mangu PB, Beck LN, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013;31:2500-10. Crossref

3. Chung JP, Haines CJ, Kong GW. Sperm cryopreservation for Chinese male cancer patients: a 17-year retrospective analysis in an assisted reproductive unit in Hong Kong. Hong Kong Med J 2013;19:525-30. Crossref

4. Rosen A, Rodriguez-Wallberg KA, Rosenzweig L. Psychosocial distress in young cancer survivors. Sem Oncol Nurs 2009;25:268-77. Crossref

5. Gorman JR, Bailey S, Pierce JP, Su HI. How do you feel about fertility and parenthood? The voices of young female cancer survivors. J Cancer Surviv 2012;6:200-9. Crossref

6. Canada AL, Schover LR. The psychosocial impact of interrupted childbearing in long-term female cancer survivors. Psychooncology 2012;21:134-43. Crossref

7. Partridge AH, Gelber S, Peppercorn J, et al. Web-based survey of fertility issues in young women with breast cancer. J Clin Oncol 2004;22:4174-83. Crossref

8. Ruddy KJ, Gelber SI, Tamimi RM, et al. Prospective study of fertility concerns and preservation strategies in young women with breast cancer. J Clin Oncol 2014;32:1151-6. Crossref

9. Senkus E, Gomez H, Dirix L, et al. Attitudes of young patients with breast cancer toward fertility loss related to adjuvant systemic therapies. EORTC study 10002 BIG 3-98. Psychooncology 2014;23:173-82. Crossref

10. Chung J, Lao T, Li T. Evaluation of the awareness of, attitude to, and knowledge about fertility preservation in cancer patients among clinical practitioners in Hong Kong. Hong Kong Med J 2017;23:556-61. Crossref

11. Lambertini M, Del Mastro L, Pescio MC, et al. Cancer and fertility preservation: international recommendations from an expert meeting. BMC Med 2016;14:1. Crossref