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The management of breast cancer depends on the type of tumour and its size or spread at discovery, but there are other markers of the aggressiveness, tumourigenic capacity or invasiveness. These characteristics are now being identified by studying the genetic profile of tumour. This process, using microarray RNA probes and polymerase chain reactions for gene profiling, allows the tumour’s fingerprint or its invasiveness gene signature to be established. Particular genes are found more or less commonly in each tumour and each one’s prevalence is called its expression. Seldom is a single gene overexpressed to give a tumour its aggressive characteristics, but rather a set of hundreds of genes whose combined expression gives clues to its invasiveness. One exceptional gene in breast cancer is the HER2 growth factor gene that is overexpressed in about 20% of all breast tumours and is associated with a poor prognosis. This has attracted publicity because the drug company, Roche, has produced a human monoclonal antibody against a particular domain of the gene that is proving an effective but controversial addition to treatment. The antibody is trastuzumab (Herceptin), and the latest report after a 2-year follow up is now published by Smith et al. (Lancet 2007;309:29–36). It is controversial in that it is very expensive; it is only used in patients who have early HER2-positive disease; it has adverse effects; and the long-term effects of monoclonal antibody therapy are not known. It is given after surgery, radiotherapy and/or chemotherapy every 3 weeks for at least 1 year. This is a formidable regimen against an aggressive tumour, but the results are significant, with those receiving Herceptin having a hazard ratio for the risk of death of 0.66 compared with observation alone after 2 years of follow up. Generally though, most information about a tumour is derived from measuring the expression of a set of its genes rather than a single gene. Which genes are present and the degree of their expression gives each neoplasm its invasiveness genetic signature (IGS). This term IGS was coined by Liu et al. (N Engl J Med 2007;356:217–26) who looked at the expression of 186 genes in breast cancer tumours and matched them with the outcomes. They found that it was not only the overexpression of some genes but also the underexpression of others that was linked to invasiveness. It has been a formidable task to identify which genes to check and how to link each to a positive or negative influence of invasiveness. The exact genes measured may change with experience, but the authors’ results showed high correlations between each tumour’s IGS and the woman’s clinical outcome. They stratified the tumours into two groups according to their IGS and found that 10-year metastasis-free survival rates were 81% in the good prognosis group and 57% in the poor prognosis group. It also allowed them to identify 90% of patients in whom metastases would occur. It is a major breakthrough in ‘bench to bedside’ research and moves us closer to delivering ‘molecular staging’ of malignancies. In countries where highly active antiretroviral therapy (HAART) is freely available, the prognosis for a person living with HIV is similar to that of someone with type 1 diabetes (Lohse et al., Ann Intern Med 2007;146:87–95). A Danish survey shows that HAART remains effective over time, despite fears of adverse effects and multidrug resistance, so there is an encouraging message for HIV-positive people in countries that have the resources and the political will to provide treatment. The days of pre-test counselling prior to HIV testing are numbered. In fact, for HIV to be treated as an exceptional disease makes it more special and probably increases stigmatisation, so most authorities no longer demand it. Frith (BMJ 2007;334:243–5) argues that this emancipated attitude should be taken further to include self-testing for HIV. The UK is pushing patient autonomy and asking people to take responsibility for their own health. This includes presenting themselves for screening, so surely the legalising of self-testing for HIV is compatible with such responsible behaviour? Suggestions that people would be incapable of carrying out the test or reading the results appear unfounded, judging from studies in the USA and false-positives will, like all positive results, need professional confirmation. The narrow view of HIV as a dreaded, prejudice-ridden disease needs to change, and the UK government has the opportunity to come up with an enlightened response to HIV self-testing. It appears that circumcised men have about half the risk of uncircumcised men when it comes to acquiring HIV through vaginal intercourse. Two trials in Kenya and Uganda were halted when interim reports showed greater than 50% reduction in risk (Rohr, BMJ 2007;334:11). The Langerhans cells of the foreskin are particularly vulnerable to HIV penetration, which is thought to explain the protection offered by their removal. These findings will probably persuade health authorities to make circumcision more widely available in countries with high HIV prevalence rates. The official definition of menorrhagia is the loss of more than 80 ml blood per regular cycle. The condition is debilitating although seldom life-threatening, and attitudes to the management have changed considerably from surgical to medical approaches, with the range of both possibilities expanding to the point where ‘hysterectomy must be the last option’ (Mayor, BMJ 2007;334:175). The UK National Institute for Health and Clinical Excellence (NICE) produces Clinical Guidelines, and their suggestions for the management of heavy menstrual bleeding make interesting reading (www.nice.org.uk/CG44). where uterine pathology is excluded, the first-line treatment they recommend is the levonorgestrel-releasing intrauterine system second-line medical options are tranexamic acid, nonsteroidal anti-inflammatory drugs or combined oral contraceptives, followed by norethisterone (15 mg daily cyclically from days 5–26) or depo-injectable progesterone. The surgical options offer an array of possibilities, with dilatation and curettage firmly relegated to history. Endometrial destruction by thermal ablation, resection, laser treatment and other means are all effective but must be selected where fertility is not a major issue and where large fibroids are not symptomatic Where fibroids are present, again there are medical and surgical approaches, with GNRH agonists and mifepristone versus uterine artery occlusion by embolisation or laparoscopic interruption using clips and/or diathermy Myomectomy and hysterectomy are the classical surgical responses to fibroids, which are causing symptoms, and, again, there are different approaches to the routes and instrumentation involved. Open laparotomy, laparoscopically assisted procedures and the vaginal route are options that depend on operator skill and physical findings Specifically, the surgical management of fibroids has been compared with embolisation. A Scottish group undertook a randomised trial of embolisation versus open surgery for symptomatic fibroids and looked at economic factors, complications both short-term and a year later and quality-of-life outcomes (REST Investigators, N Engl J Med 2007;356:360–70). Their results were encouraging with similar outcomes at 12 months with symptom scores better in the surgery group but a shorter hospital stay and more rapid recovery in the embolisation group. There seems little to choose between embolisation and open surgery for fibroids, but the possibility of pregnancy arises after embolisation and obviously hysterectomy ensures the end of bleeding problems. Embolisation was first used in the early 1990s by Ravina to treat fibroids in women at high risk during surgery. Later, it was employed to reduce fibroid volume prior to myomectomy to reduce blood loss, then used for primary treatment of fibroids. More than 100 000 procedures have been carried out since them mainly in the USA and Western Europe by radiologists. Through the femoral approach, catheter access is gained to each uterine artery and standardised embolic agents 500–700 μm in size are released to occlude the arteries—not only those thought to be supplying the fibroids (Tulandi, N Engl J Med 2007;356:411–13). Complication rates are around 10%, and reports on pregnancies thereafter indicate high miscarriage and preterm labour rates, so patients have to be fully informed about these possibilities. Where pregnancy is desired and in infertile women, myomectomy still remains the treatment of choice. Embolisation has now been compared with laparoscopic occlusion of the uterine arteries (Hald et al., Obstet Gynecol 2007;109:20–7). They used a combination of occluding clips on the uterine arteries, and the utero-ovarial ligaments were coagulated with bipolar forceps, thus reducing uterine perfusion to the collateral circulation. Both techniques resulted in a greater than 50% reduction in menstrual flow as assessed by pictorial charts and patients’ perceptions. Six-month follow up also reflected comparable results, allowing the authors to state that laparoscopic occlusion is a promising method but should be, as yet, confined to expert experimental situations. The last word is that hysterectomy remains a reasonable alternative and is, after all, definitive. Preterm delivery remains the greatest cause of neonatal mortality and morbidity. The incidence is rising, and treatments have been unable to show significant benefit to the neonate. However, a Canadian trial just published may change that (Smith et al., Am J Obstet Gynecol 2007;196:37–9). Treating women who had regular painful contractions with nitroglycerin between 24 and 32 weeks showed a delay in delivery of 11 days compared with placebo. This overall result was highly significant, and the treatment appeared most effective between 24 and 28 weeks. The nitroglycerin was delivered by transdermal patch, and all patients were given steroids. Unsurprisingly, the delay resulted in measurably better neonatal outcomes in mortality and less lung disease. The number needed to treat was ten to enjoy the overall benefits. The trial was meticulous and the bottom line probably grossly understated the case when the authors say that the use of nitroglycerin ‘may result in a major cost saving and longer-term health benefits’. Watch this patch! High-profile events remind the medical professionals that they have obligations of protection. The publicity around the murder of five sex workers in one area of the UK spurred the BMJ to an enlightening editorial on the topic of protecting workers in the oldest profession. They are no doubt an at-risk group, having the highest mortality of any section of women and suffer victimisation and marginalisation. In addition, countries like the UK have antiquated laws discriminating against sex workers that confuse morality and legislation. Goodyear and Cusick (BMJ, 2007;334:52–3) assert that the law should protect workers, irrespective of the perceived morality of their trade and that prostitution should be removed from criminal law. They label the status quo ‘unacceptable moral cowardice’ and challenge politicians to follow the example of New Zealand whose Prime Minister, Helen Clark, legislated to decriminalise sex work in 2003. She said that the move was for the welfare of a vulnerable group and not related to morality. A correspondent to the BMJ takes the argument several steps further. Owens (2007;334:170) suggests that sex workers raise their client’s self-esteem, especially if they come from the less fortunate strata of society. They could also use their skills in participating in the recovery of stroke victims. They certainly are masters, or the female equivalent, of nonverbal communication.

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