In 1961 Mary-Claire King was just fifteen when she watched her best friend die of a kidney tumour. She recalls, “Her death was devastating. It seemed so unfair. It wasn’t a conscious decision, but I said to myself, something needs to be done. It’s the little pebbles that make a path.” King’s youthful determination led to a spectacular breakthrough thirty years later when she was a distinguished professor of genetics at the University of California at Berkeley.

In a seminal paper, published in Science in 1990, King and her colleagues provided evidence for the existence of the first gene for hereditary breast cancer. They showed that chromosome 17 was the locale of a gene — later named BRCA, short for BReast CAncer — for inherited susceptibility in families with early-onset disease. King’s research transformed the field, enabling the gene to be cloned and the development of a simple diagnostic test.

Earlier this week the actress Angelina Jolie wrote an op-ed piece in The New York Times, revealing that she had undergone a double mastectomy earlier this year despite the absence of breast cancer. Her mother had died of ovarian cancer at age 56 and Jolie, having been diagnosed with the faulty BRCA1 gene, decided on prophylactic surgery. Her doctors estimated she had an 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer. “Once I knew that this was my reality,” she said, “I decided to be proactive and to minimize the risk as much as I could.”

Angelina Jolie. Copyright: USA Today.

Jolie described in considerable detail the surgical procedures, including the subsequent reconstruction of her breasts with implants, commenting that her choice did not in any way diminish her femininity. She stated that her chances of developing breast cancer had fallen to less than 5 percent, and concluded: “Life comes with many challenges. The ones that should not scare us are the ones we can take on and take control of.”

Perhaps unsurprisingly, news of Jolie’s decision generated considerable debate. Myriad Genetics, the company that developed the diagnostic test and is now facing a legal challenge to its monopoly in the US Supreme Court, saw its stock rise after the announcement. A recent paper in the Journal of the American Medical Association has shown that prophylactic mastectomy does indeed reduce the risk significantly. It’s intriguing to think how one woman’s discovery almost a quarter of a century ago led to another woman’s decision to take control of her own destiny.

Yesterday the Cancer Council in Australia announced that the country was gaining the upper hand in the war against cancer, with 60,000 lives saved over a two-decade period. They attributed their success to three factors: prevention, screening and treatment. One of the issues identified was obesity — a major risk factor for bowel and breast cancer — and the Council suggested that weight reduction programmes had contributed to the improved statistics. This begs the question: can exercise lower breast cancer risk?

In a study published last year in the Journal of Clinical Oncology, researchers from Seattle showed that women who exercised and dieted to lose a moderate amount of weight also experienced a reduction in their oestrogen levels and other hormones associated with increased breast cancer risk. They studied 439 overweight and post-menopausal women aged 50 to 75 who were sedentary, and divided them into four groups: (1) a diet group who cut out sugary beverages and desserts while increasing fruit, vegetables and fibre; (2) an exercise group who did five 45-minute aerobics classes per week; (3) a group who both dieted and engaged in brisk walking; and (4) a control group who made no change to their diet or exercise habits.

At the completion of the 12-month study, groups 1 and 3 saw the greatest benefit, having dropped an average 10% of their starting weight, and also experienced a statistically significant reduction in their oestrogen levels and other hormones. Anne McTiernan and her co-authors estimated that a 5% weight loss may reduce a woman’s breast cancer risk by 22%. Interestingly, women in group 2 who exercised but failed to lose weight did not lower their hormone levels.

Another study, just published in Cancer Epidemiology, Biomarkers & Prevention, by researchers from the University of Minnesota reported that women who exercised five times a week for 16 weeks demonstrated changes in their oestrogen metabolism. “Ours is the first study to show that aerobic exercise influences the way our bodies break down oestrogens to produce more of the ‘good’ metabolites that lower breast cancer risk,” said lead author, Mindy Kurzer.

Can the findings from these two studies be reconciled? Perhaps they can. Although exercise may not lower oestrogen levels per se, it does appear to change the break down of oestrogen and modify the metabolites that, in turn, reduce the risk of breast cancer. This is good news for women who are willing to make the effort and exercise.

Sixty years ago, three Soviet scientists published a paper, in Russian, entitled “Study of electronic emission during the stripping of a layer of high polymer from glass in a vacuum.” They demonstrated that a process called triboluminescence — where relative motion between two contacting surfaces produces visible light — converts mechanical energy into electromagnetic radiation, including X-rays. As often happens in the history of science, this phenomenon lay dormant for over fifty years until 2008 when a group of physicists from the University of California at Los Angeles (UCLA) published an article in Nature entitled “Correlation between nanosecond X-ray flashes and stick-slip friction in peeling tape.”

Like all good entrepreneurs, the researchers filed a provisional patent before publication and assigned the intellectual property to their employer. Three years ago one of the inventors, Carlos Camara, formed a company called Tribogenics to commercialise the metal-polymer technology which they licensed from UCLA. Their small powerful X-ray sources are scalable and can be configured as single point emitters or clustered into flat-panel arrays of X-ray pixels that can be individually addressed. Since the fragile glass tube and high voltages have been eliminated, these X-ray sources are apparently safe to use in any environment.

Carlos Camara holds a tiny X-ray emitter

So how does the technology work? According to the authors, “As the tape peels off, the sticky acrylic adhesive becomes positively charged and the polyethylene roll becomes negatively charged, so that electric fields build up to values that trigger discharges. At a reduced pressure, the discharges accelerate electrons to energies that generate Bremsstrahlung X-rays when they strike the positive side of the tape.” While there are experts like Ken Suslick at the University of Illinois who are skeptical that so much of the mechanical energy can be transformed into X-rays, Camara and his team at Tribogenics are pushing ahead regardless.

It’s an interesting thought that at some stage in the future, an experiment performed with an off-the-shelf roll of Scotch Tape mounted on ball bearings in a vacuum chamber could lead to a miniature X-ray source that will aid in the diagnosis of breast cancer.

Dr Sarah Steenbergen. Copyright GetInsideHealth.

In the late 1950s researchers at ICI Pharmaceuticals in the UK were actively looking for a class of anti-oestrogen compounds, hoping to developing a morning-after contraceptive pill. Arthur Walpole and his team synthesised tamoxifen, a drug that has subsequently become the endocrine treatment most widely used in breast cancer, both in adjuvant therapy and for advanced disease. Earlier this week a paper appeared in the Journal of Clinical Oncology showing that if women who are being treated with tamoxifen see a decrease in their breast density, they have a 50% lower risk of dying from breast cancer.

Dr Per Hall. Copyright Karolinska Institutet.

The research team was led by Per Hall at the Karolinska Institutet in Sweden who followed almost a thousand patients over a 15-year period. “To the best of our knowledge, this is the first time mammographic density change has been used as a prognostic marker of response to tamoxifen,” wrote Hall and colleagues. Measuring the change in breast density could therefore be a simple and effective method for assessing whether a drug is working or not.

These findings by the groups in Connecticut and Stockholm, which are supported by a recent paper in Clinical Imaging by Vincenzo and Concetta Giuliano, suggest the need for a screening tool that incorporates both full-field digital mammography and automated breast ultrasound in a single instrument. At CapeRay we are currently building such a device — our dual-modality Aceso model — that will be clinically tested later this year.

There are distinct parallels with the reality television programme Dragons’ Den that features entrepreneurs who pitch their business ideas to a panel of VCs in order to secure investment finance. The contestants are often product designers who try to convince wealthy businessmen and women — the eponymous “dragons” — to invest money in exchange for a percentage of the company’s shares. The dragons ask probing questions and, more often than not, the entrepreneur walks away empty-handed. The format is clearly successful as there are now two-dozen versions of the programme around the world.

At the Dublin meeting there were 43 companies pitching their investment opportunity to 32 VC and private equity firms. Each of us had just ten minutes to make our case, to explore the answers to questions such as: What is the problem we are solving? What are the benefits of our solution? How large is the market opportunity? The format differed from Dragons’ Den in that the VC firms initiated their due diligence after our presentations in one-on-one meetings rather than during the plenary session. Much less stressful!

This was an international event with start-up companies like Calon Cardio from Wales, FBC Device from Denmark and Aerogen from Ireland. The VC firms also covered a wide geographic area, with Abingworth from the UK, Gilde from the Netherlands and Lighthouse from the USA. CapeRay was one of three diagnostic imaging companies represented, while there were two other companies with novel breast cancer products. Chronix from California has developed a real-time diagnostic blood test that is used by the oncologist during treatment, and MitaMed from Ireland utilises an energy-based technology called electroporation to treat solid tumours.

Was this a successful event for CapeRay? Simply stated, “Yes”. We have initiated discussions with potential investors and partners and, most importantly, we learned a great deal about the VC landscape.

Securing regulatory approval from the FDA is the sine qua non for any medical device company that seeks to market and sell its products in the USA. There are two approaches by which this approval can be achieved: pre-market approval (PMA), a sometimes lengthy process requiring extensive clinical trials; and the so-called 510(k) approach, where a company’s new product needs to demonstrate equivalence to a predicate device.

In justifying the increase in the CDHR’s budget, the agency has set some performance benchmarks for itself, with the aim of reviewing and deciding on 80% of PMA applications within 180 days of filing and 93% of 510(k) submissions within 90 days. This is good news for companies like CapeRay that need to release their products into the market within a reasonable time period.

FDA Commissioner, Dr Margaret Hamburg.

“These are tight budget times, and the FDA budget request reflects this reality,” said the FDA Commissioner, Margaret Hamburg. “Our budget increases are targeted at strategic areas that will benefit patients and consumers and overall strengthen our economy. Through the good work of the FDA, Americans will receive life-saving medicines and devices approved as fast as or faster than anywhere in the world, confident in the medical products they rely on daily.”

The FDA’s history is an interesting one, dating back to the late 19th century, in the period after the Civil War. A landmark piece of legislation that launched the agency was the Pure Food and Drug Act of 1906, prohibiting interstate commerce in misbranded and adulterated food and drugs. For over a century the FDA has sought to balance the need to protect the American consumer, on the one hand, with the desire of those same consumers to have access to the latest and most innovative medical technologies.

The success of TV shows like House and Grey’s Anatomy, the latter a focus of last week’s blog, shows there’s a hunger among the general public for medical storytelling. One artistic medium that lends itself to telling stories is the comic strip, emerging into popular culture during the 19th century. An illustrator, Ray Rieck, and a physician, Dr Michael J Green, have recently collaborated on a comic strip called “Missed It” that was published in Annals of Internal Medicine.

“First time I’ve been published in a medical journal — not something I was ever anticipating” said Rieck. “It all stems from my work with a medical ethicist at Penn State who’s one of the pioneers in a sub-field of medicine that uses comics and graphic novels to aid in doctor/patient understanding.” The basis for the story is a real case that confronted Dr Green twenty years ago when he was an inexperienced intern on night call.

All images copyright: Annals of Internal Medicine.

Green is woken at 3:00 am by a fellow registrar who tells him that a patient with chronic obstructive pulmonary disease (COPD) has been admitted to the emergency room. Shaking off his drowsiness, Green makes his way down to the ER, thinking this will be a straightforward case, with the patient simply requiring a nebulizer, steroids and some oxygen. Upon examining the patient, he discovers a heart murmur but the registrar he’s relieving tells him not to worry, “It’s old, documented in the chart.” Green writes the admission order, takes his patient upstairs to the ward, and goes back to bed.

However, all is not well. The nurses call him at 4:30 am and report that the patient is struggling to breathe. Green rushes back to the ward and reviews the notes, discovering that his patient is not a smoker, the chest X-ray looks fine, the nebulizer is not working and concludes that COPD was probably the wrong diagnosis. Before he is able to move his patient to the intensive care unit, the 54-year-old man suffers a massive cardiac arrest and dies. An autopsy confirms the cause of death: pinpoint aortic stenosis. The young doctor is devastated.

“It was a very difficult situation, and it happened a long time ago, but it haunted me for a long time, and I knew it was something I wanted to write about at some point,” Green said. Comics are a powerful way to communicate as this story so graphically illustrates.

The appearance of Statscan on the show was a major marketing coup for Lodox. According to CEO, Pieter de Beer, immediately after the show aired Lodox was “receiving approximately 40 hits per minute on its website, ongoing for the past five hours!” At CapeRay we were intrigued to find out how our sister company — we share the same investor, the IDC — was able to achieve such worldwide exposure.

The creators of Grey’s Anatomy pride themselves on producing a show that is based on authentic medical practice. In January their researchers visited the emergency room (ER) at Los Angeles County Hospital where they saw the Statscan in operation. They contacted Marty Kulis of Lodox’s North American office who responded immediately and agreed to loan a machine to the fictitious Grey-Sloan Memorial Hospital for the duration of Season 9. According to Dr Sarah Whiley, product manager at Lodox, “We did not have to pay anything for this opportunity except the costs of getting the machine to set. We also had no input on how the machine was used in the episode, or the script. However, we did provide the full-body images that they show”.

In the episode a member of Dr Hunt’s team volunteers to have her body scanned, telling everyone that when she was six she had stuck a marble up her nose that had never been recovered. The chief surgeon admonishes her, saying the machine is not a toy and should be ready for any emergency. It transpires that in real life the Statscan was recently used in an ER in Bern, Switzerland to identify a foreign object — which turned out to be a razor — that had been ingested by a psychiatrically disturbed patient.

We are delighted at the recognition given to Lodox and wish them every success in bringing their cutting-edge technology to emergency rooms around the world.

The organisation grew steadily, reaching into many countries and offering a programme of different services: support, education and advocacy, all aimed at improving the lives of patients. For the past three days almost 400 delegates — over 80% of them survivors of breast cancer — have been meeting in Cape Town for the 17th Reach to Recovery International Breast Cancer Support Conference. Their theme has been “Together We Reach” and a strong focus has been on Africa, symbolised by the conference logo that features two arms embracing a pink Protea (see above).

Among the keynote speakers was Musa Mayer from the USA, a 23-year survivor of breast cancer who for the past two decades has been a tireless advocate for women living with breast cancer. Among the books she’s authored are After Breast Cancer: Answers to the Questions You’re Afraid to Ask and Holding Tight, Letting Go: Living with Metastatic Breast Cancer. She spoke about this latter topic, emphasising that while life with “mets” remained a challenge for patients, even in well-resourced countries, the last thing these women wanted was to be “hidden and forgotten”.

Another of the outstanding plenary lectures was delivered by Dr Carol Benn, one of South Africa’s foremost breast surgeons who spoke about the power of advocacy. Her theme was based on “The Big Five”: education (I am Lion, hear me roar); diagnosis and screening (I am Leopard, know me by my spots); treatment (I am Buffalo, with a mean and hungry look); support (I am Elephant, I never forget); and service (I am Rhino, please save me).

The Mother City has been privileged to host this uplifting event where women have come together to share their personal stories. Fittingly, at the closing ceremony Adri van Nieuwenhuizen, a lyricist who was diagnosed with breast cancer in 2005, sang Because of You, a song inspired by Reach for Recovery.

The book brings five key points into sharp focus. First, it provides the historical context of the 1960s and 70s when screening mammography was first rolled out in the USA, showing that it was inevitable the test would be dogged by controversy. Second, it describes how political forces and social movements had a substantial influence on the culture of screening mammography. Third, the book illustrates the dominant role of politics, eventually trumping science itself. Fourth, The Big Squeeze describes the economic impact of screening, with the mundane mammogram becoming “the little pink engine that could, and did, drive the growth of a vast screening-dependent secondary economy”.

Finally, Reynolds considers one of mammography’s major drawbacks — overdiagnosis. This phenomenon, where screening uncovers a cancer that would otherwise never have been identified in a person’s lifetime, inevitably leads to overtreatment as highlighted in our recent blog. Chapter headings include: Timing is Everything; First Exposure; The Aftermath; A Tale of Two Epidemics; Age is Nothing But a Number; Pulling the Plug on Granny; The House that Mammography Built; and Overdiagnosis: Mammography’s Burden.

The crusade of American women seeking greater access to screening was boosted by the news that the wives of two incumbent Presidents, Betty Ford and Nancy Reagan, were diagnosed with breast cancer while they and their husbands occupied the White House. Politics played a role elsewhere. In alliance were the American Cancer Society and the American College of Radiology, with a clear vested interest in favour of screening, while taking a more dispassionate but contrary view were two Federal agencies, the National Cancer Institute and the US Preventive Services Task Force.

Reynolds believes “the position of screening mammography is secure until a replacement technology comes along”. The Big Squeeze is just 114 pages long in hardcopy format but is well written and will serve as an educational resource for both clinicians and patients alike.