New Ways to Beat Breast Cancer

On a pleasant August evening in 2015, Ruhaila Jalal Khan, 53, was enjoying the view of the valley when she first felt a lump in her left breast. A resident of Anantnag, in Jammu and Kashmir, Ruhaila performed a breast self-exam every week. She visited her doctor the very next day, who reassured her but suggested a mammogram. "The mammogram did not reveal anything but I wasn't convinced. Four doctors and many tests later, a biopsy confirmed my worst fears," she says. And suddenly Ruhaila, a mother of two, found herself thrust into a vast club she would much rather not be a part of: women with breast cancer.

An estimated one in every eight women around the world will develop the disease in their lifetime, with the latest statistics indicating that 1.7 million globally were diagnosed in 2012 alone. According to the Indian Council of Medical Research, breast cancer was the most common cancer among women in India last year, with 1.5 lakh new cases in 2016 alone, affecting 1.45 lakh females (and 0.05 lakh males).

Considering Ruhaila's profile, doctors recommended the standard medical approach: Remove the whole breast or at least a part of it, use radiation and then, if the tumour is really aggressive, use chemotherapy, making the overall treatment a trifecta for side effects such as nausea, hair loss and brain fog. Luckily for Ruhaila, her cancer was detected early. This gave her another critical option: a genomic test of the tumour to assess the risk of it reappearing and plan the treatment accordingly.

"Self awareness and a yearly mammography after 40 years of age is the gold standard for the early detection of breast cancer worldwide. The treatment has three components -- surgery, drugs and radiation. Today, the focus is no longer on removing the entire breast and the lymph nodes but a more personalized and targeted treatment, depending on the type of breast cancer," says Dr Sidharth Sahni, senior consultant breast surgeon, institutes of cancer, Indraprastha Apollo Hospitals, New Delhi.

"In the past 15 or 20 years, breast conservation has been a major positive development in India. One that offers better quality of life for patients," says Dr Sudeep Gupta, deputy director, Clinical Research Centre -- Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Mumbai.

But new discoveries and innovations are paving the way for better patient care today. Take for example the MasSpec Pen -- a handheld mass spectrometry system -- a breakthrough revealed in a paper in the journal Science Translational Medicine last month. "One of the challenges of a breast conserving surgery is the balance between removing too much and not enough of the tissue. With the MasSpec Pen this is easily achieved, and it takes less than 10 seconds to do it," adds Sahni.

About 50 years ago, scientists thought most tumours were alike and there were few treatment options outside of surgery, radiotherapy and chemotherapy. In the '70s the 10-year survival rate was around one in four, but 50 per cent of patients who were diagnosed in 2010-11 will survive for 10 years. Back then, in the first glimmer of exciting changes to come, doctors began to test 'precision' drugs like tamoxifen and then trastuzumab, a laboratory-produced antibody treatment better known by its brand name, Herceptin, which can stop cancer cells from growing.

Today, thanks to advances in genetic testing, we know even more about breast cancer. A landmark 2012 study undertaken by scientists at Cancer Research UK Cambridge Institute, for example, proved that the disease can be divided into 10 different sub-groups, each of which may respond to different combinations of drugs, non-invasive treatments, surgery or, in the case of tumours that grow really slowly, no treatment at all. We know about gene mutations, both acquired and inherited, and the possible effects of hormonal levels and smoking on developing cancer. At this stage, there is also clear evidence that alcohol consumption, excess weight and lack of exercise increases this risk of developing breast cancer.

"We are continuing to develop methods to detect tumours earlier, and to find new telltale markers in order to help doctors better tailor treatment," says Dr Aine McCarthy, the organization's senior science information officer. When physicians know exactly what they're dealing with, be it an ER positive tumour (which grows in response to female hormones), for example, or a HER2 positive tumour (one which has large amounts of the human epidermal growth factor receptor 2 protein on the surface of the cancer cells), it makes all the difference in helping doctors develop a treatment plan. An international study published in May 2016 in the journal Nature examined in minute detail the genomes in 560 breast cancers, sifting through billions of letters of code to find the mutations in each case. While this research led by the Wellcome Trust Sanger Institute in Cambridge, UK, is not a new cure, it represents a giant leap towards treatment that is tailored, not just for a specific kind of cancer, but for each patient.

"All cancers are due to mutations that occur in all of us in the DNA of our cells during the course of our lifetimes," said Professor Sir Mike Stratton, director of the Wellcome Trust Sanger Institute. "This study brings us much closer to a complete description of the changes in DNA in breast cancer and thus to a comprehensive understanding of the causes of the disease and the opportunities for new treatments."

"A detailed pathological characterization of the tumour at a genomic level has led to more focused and targeted treatment. Although this has enhanced our understanding of the tumour, it has not yet led to change in treatment strategies for most patients in India. We hope that it will in the near future," says Gupta.

Says Ruhaila: "In September 2015, we went to Delhi for treatment. I was recommended chemotherapy but my doctor told me about a test that could reveal if I would actually benefit from it." She opted for the Oncotype DX, a genomic test done post-surgery that assessed the risk of the cancer recurring and the effectiveness of chemotherapy, and later her samples were sent to the US. Done exclusively in centralized labs in the USA or the Netherlands, genomic tests like the Oncotype DX, MammaPrint or Prosigna have prognostic and predictive value, says her physician Dr Kanchan Kaur, associate director, breast services, Medanta-The Medicity, Gurugram. "The tumour turned out to be low-risk so we avoided chemotherapy and I underwent a breast conservation surgery with radiotherapy," says Ruhaila. The test was expensive -- about Rs 4 lakh -- however it was worth it, as after about five months of treatment, she was cancer-free. By avoiding chemotherapy Ruhaila and those with early stage cancer can skip all pernicious side effects -- nausea to infections to cognitive health problems -- of chemotherapy.

Breast cancer is a specific diagnosis but it behaves differently in different women as it is an amalgam of different types of cancers under the broad umbrella of 'breast cancer'. "Tests like Oncotype DX are valid for those women who have small breast cancers that are hormone receptor positive. It is only used for lymph node negative patients. This test evaluates about 21 genes that can influence how the cancer will respond to treatment and whether it will recur," says Sahni.

Patient, Heal Thyself           

The immune system is a mysterious thing that can swoop in to heal your common cold and cause autoimmune conditions such as arthritis and type I diabetes. Now, researchers like Dr Pam Ohashi, director of the tumour immunotherapy programme at the Princess Margaret Cancer Centre in Toronto, are trying to harness its power to combat breast cancer. The idea is to stimulate one's own immune system to work harder and attack cancer cells.

"There are these molecules called 'checkpoint inhibitors' that act as stop signals and regulate the immune system," explains Ohashi. Clinical trials in certain types of cancer that naturally induce a strong immune response -- such as melanoma -- have tested drugs that block these negative signals and release the body's T cells, the foot soldiers of the immune system, to go fight tumours.

In India, the discovery of cancer antigen SPAG9 by Dr Anil K. Suri, translational cancer researcher and director, National Institute of Immunology, New Delhi, an autonomous institute of the department of biotechnology, Ministry of Science and Technology, has already set the wheels of change in motion.

This antigen (SPAG9) was discovered while working on Indian cancer patients and some experts think it will revolutionize breast cancer diagnosis and treatment. It is an antigen that is expressed in the early stages of breast cancer. "The antibodies against this molecule are detected in the blood of stages I and II breast cancer patients when it is still confined to the breast and has not metastasized. This has implications on early detection, diagnosis and treatment of the cancer," says Suri.

"If detected early, the survival rate for breast cancer patients can be more than 90 per cent. However, due to lack of awareness and unavailability of medical infrastructure, most patients only walk into the clinic when the disease has advanced, and as such the prognosis tends to be poor," he says. Soon all it will take is a simple blood test -- a much less invasive detection method. "With patents in place, large-scale validation of the study is underway. By examining a drop of blood for antibodies against SPAG9, doctors can screen patients and suggest further tests and treatment. A cost-effective test such as this will make a big difference in India," Suri adds. With clinical trials in the pipeline, it may provide hope to thousands of patients.

An immunotherapeutic vaccine for breast cancer is the next step. "The goal is to use the patient's own immune cells to fight the cancer. We can reactivate the immune system by developing dendritic cells derived from the patient's own blood cells and prime them with the SPAG9 antigen and then inject the mature primed dendritic cells back to the patient. This way we can customize cancer treatment. There will be no side effects or no off-target effects on normal tissues and no toxicity. Efforts are on to release this as early as possible, and for this we are collaborating with Dr T. Rajkumar, medical oncologist and molecular oncologist at Cancer Institute (WIA), Adyar, Chennai," says Suri.

"The notion of using the immune system to treat cancer has shown unprecedented success," Ohashi says. "Combined with other strategies, it has the potential to cure cancer. That could be 10 years down the road, but the time has now come to think of it as a reality."

Cooling Things Down

The idea is simple: Cool a tumour and the surrounding tissue to the point that the cells within freeze, let the cells burst their cell boundaries or 'pop' like a full can of frozen soft drink, and after the malignant ones rupture they are harmlessly reabsorbed into the tissue. An Israeli invention, the IceSense3 machine, which requires a needle to be inserted into the breast tumour, is being tested in patient trials across 20 sites in the USA and one in Japan. It is yet to be available in India.

Already successful in kidney, liver and lung cancer treatments, the procedure, which is currently limited to women aged 65 and above with breast tumours that are no more than one and a half centimetres in diameter, takes up to a half-hour and requires only a local anaesthetic.

"You turn the machine on once the needle is placed, and the needle gets cold in about 20 seconds," says Will Irby, vice-president at the Memphis-based IceCure Medical Inc in the USA. "The tumour is frozen from the inside out and you can watch the ice ball being formed with the help of an ultrasound."

Dr Richard Fine, director of education and research at the Margaret West Comprehensive Breast Center in Memphis, notes the procedure is non-surgical, and its goal is to replace surgical treatment. Additional treatments such as radiation may be recommended on a case-by-case basis. "The patient will still feel a lump for about six months, as the dead cells are being re-absorbed and the changes caused by the cryo-ablation are being resolved," he says.

For New Jersey resident Muriel Smith, having the procedure in February 2016 was 'a piece of cake' -- she hopped off the table at the medical centre, donned her shirt and went off to a lunch date. "At my age, I'm not really crazy about going under anaesthesia," says the 80-year-old. Forty-seven days after the diagnosis, she was free of cancer. Muriel now has to have a mammogram each year for the next five years.

Heating Things Up

For preferential radio frequency ablation, or PRFA -- a procedure that Margareta Nordell, 72, from Stockholm went through in 2011 -- the physician first carefully guides a needle into the tumour with the help of an ultrasound machine and then secures it in place and delivers energy to burn the tumour using mechanical micropulses. Following that, the cancer cells trying to escape through the tumour's blood vessels are quickly killed off by the electric pulses in a process called anti-seeding.

Once positioned correctly, an electric current is then conducted through the tissue via the needle, resulting in mechanical friction that quickly heats the cells up and kills or damages them depending on the temperature -- when these cells scatter, they don't grow, and therefore they can do no damage, says Hans Wiksell, a professor emeritus at Stockholm's Karolinska Institutet who is also the lead scientist on the project and built the PRFA machine. The electrode needle brings the central body of the tumour to 70 degrees C, which quickly kills all the cells within, while the temperature in the zone immediately outside of the tumour is ideally 43 degrees C, where non-cancerous cells can repair the damage but cancerous ones will not.

"In India it is used only for tumours of less than three centimetres and primarily for cancers that have metastasized mainly to the liver," says Gupta. "The wonderful thing is that the precision and control create a completely different mechanism to treat breast cancer," Professor Wiksell adds. "You can get cancer from chemotherapy and radiation. Nuclear bombs can cause cancer but heat can't."

So far, the trial has tested the procedure on 18 older patients, including Margareta, and has boasted a high success rate. The trial is limited because older patients tend to have tumours that aren't as virulent and fast-spreading as those in younger ones. As for Margareta, at first she was a bit startled by all the fuss in the operating room. Then she closed her eyes and barely 20 minutes later, it was all over. Margareta has now been cancer-free for six years.

Closer home, a cheerful Ruhaila says: "I'm very lucky to have been detected early and grateful that I avoided chemotherapy. Thankfully, everything is okay now and I can be there for my family. I feel blessed."