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Breast Cancer

RETHINKING BREAST CANCER TREATMENT
 
It’s October again and we are being bombarded with a great deal of hype about the risks and dangers of getting breast cancer. After the NZ Herald featured an article about a 23-year-old woman who was diagnosed with DCIS (ductal carcinoma in situ) and had a mastectomy, it was refreshing to see the 12 October issue of TIME magazine feature an article on why doctors are rethinking breast cancer treatment. The article addresses the thorny issue of the overdiagnosis and overtreatment of DCIS and how women are being subjected to “too much chemo, too much radiation, and way too many mastectomies.” (1)
 
DCIS is now usually referred to as early stage breast cancer when it is not, as it is non-invasive, found only inside the milk ducts and not in the surrounding breast tissue. In his book “Mammography Screening: truth, lies and controversy,” Peter Gotzsche writes:
“Much of what we call breast cancer is not even a disease, but cell changes that women do not benefit from having detected and treated.” (2)
 
DCIS once accounted for about 3% of breast cancers detected as a result of breast cancer screening but now accounts for around one in four so-called breast cancers.
 
“Now those at the vanguard of breast cancer treatment are calling for a major shift in the way doctors treat – and talk about – the disease, from the first few millimetres of suspicious-looking cells in milk ducts to the invasive masses found outside of them. That’s making the tough conversations between a woman and her cancer doctor even harder, but it also stands to make them more fruitful.
 
Because as good as we have gotten at finding breast cancer – and we have gotten very good – all this new data suggests there may be better ways to treat some breast cancers, particularly those at the early stage. Evidence is mounting that aggressive treatments, designed in earnest to save women’s lives, can have unforeseen and sometimes devastating consequences.
 
Call it collateral damage. It’s the multiple follow-up surgeries after a mastectomy and the subsequent infections; the radiation that doesn’t always improve survival and the cancer risk that can come with too much of it; the sometimes unnecessary chemotherapy and its life-sapping effects. For some in the field, that collateral damage is getting harder and harder to justify.” (1)
 
The overdiagnosis of DCIS as breast cancer is wide spread and causes a considerable amount of harm. Peter Gotzsche describes it like this: “This result is alarming. Not only because these women will have to live the rest of their lives as cancer patients, fearing that the ‘pseudo-disease’ – which never was a disease and never would have been were it not for screening - would come back and kill them, but also because some women die from the unnecessary treatment. It is a new ethical dilemma in healthcare that some people will have to pay with their lives to enable others to live longer.” (2)
 
Like Gotzsche, Siobhan O’Connor, the author of the TIME article, thinks cancer has a language problem. It’s the war metaphors we use when we refer to the battle against cancer. Richard Nixon declared war against cancer over 40 years ago and others have followed in his footsteps, but it is “a war that drafts soldiers who never signed up for it, who do battle and win, or do battle and lose.” (1)
 
In 2015 a diagnosis of breast cancer is not necessarily a death sentence or the beginning of the end. While increasing numbers of women are being diagnosed with breast cancer, the death rate over the past 15 years or so has remained largely the same, mainly due to better treatments that are now available. 
 
Eight years ago Desiree Basila went looking for options when she was diagnosed with DCIS and told that “there was a slot open the following week for a mastectomy.” She made an appointment with another breast surgeon and spent half an hour grilling her. She was still not satisfied when the doctor recommended a lumpectomy. Frustrated she stood up and prepared to leave and then issued a half taunt, “What if I decide to just do nothing?” Only then did the doctor say “Well, some people are electing to do that.”
 
Basila sat back down and after another half an hour spent discussing other options with Dr Shelley Hwang, she elected to start taking tamoxifen, a drug that blocks oestrogen, and to enrol in a clinical trial involving active surveillance. Basila’s doctor, Dr Hwang, is now chief of breast surgery at Duke University in North Carolina, and Dr Laura Esserman, a surgeon at the University of California, are currently leading a number of studies on women who have been diagnosed with DCIS. Dr Esserman is creating a DCIS registry and launched the WISDOM study which will randomise women with DCIS to either annual screening or a more personalised screening approach. (3)
 
In the UK an investigation called LORIS is under way. Loris is a 10-year randomised controlled prospect-ive study, funded by the UK’s national Institute for Health Research, which will include 900 women. Half will get the standard care - surgery, and half will be actively monitored. (4)  
 
“My personal view is that enough time has been spent arguing about screening, and we now should be addressing the issue through well-run clinical trials that are long overdue,” says Dr Adele Francis, a breast surgeon at University Hospital Birmingham and the lead on the LORIS study. (1)
 
The other important people in this dilemma are the women with the diagnosis. “Change in medicine comes from patients,” says Dr Esserman. “My patients don’t like the options we have. So I say, Get the facts. Find someone who will go through those options with you.”
 
New Zealand women also deserve to be offered more options than surgery.
 

References:  
1. Siobhan O’Connor. “Why doctors are rethinking breast cancer treatment.” TIME 12 October 2015
2. Peter Gotzsche. “Mammography Screening: truth, lies and controversy.” Radcliffe Publishing 2012.
3. https://www.salesforce.com/blog/2015/09/wisdom-study-best-approach-breast-cancer-screening.html
4. http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-comparing-surgery-with-active-monitoring-for-low-risk-dcis-loris



IMPORTANT FACTS ABOUT BREAST CANCER
  1. Breast cancer screening programmes have not reduced breast cancer mortality rates.
  2. For the vast majority of women, the lifetime risk of dying from breast cancer is about 3%-4%.
  3. Women have more than a 50% chance of surviving breast cancer once it is diagnosed
For more information on the failure of breast cancer screening programmes to reduce the mortality rate see "Mammography Screening: Truth, Lies and Controversy" by Peter Gotzsche.  Radcliffe Publishing 2012.


The Breast Cancer Genes
On the 14th of May 2013 Angelina Jolie’s revelation that she carried the BRCA1 breast cancer gene and had had a preventative double mastectomy made world headlines and the fear of breast cancer went through the roof. Women’s support groups, health centres and health agencies were deluged with calls from fearful women who wondered if they might have either of the BRCA1 and BRCA2 genes that are associated with a high risk of breast and ovarian cancer.

In the aftermath of the publication of Angelina Jolie’s story in the New York Times (1), risk percentages for breast cancer were exaggerated and talked about as though they were death sentences. Her 87% risk of breast cancer became 90% which according to Professor Geoff Lindeman, head of the RMH Familial Cancer Centre, was “the upper end of risk when the gene was first discovered.” (2)

Only about 5% of all breast cancers are hereditary, and not all of them will involve the BRCA1 or BRCA2 gene. The risk of cancer for women with the breast cancer gene is somewhere between 40 – 65% with the risks for women with the BRCA1 gene being higher than for those with the BRCA2 gene. In the midst of the panic that was generated by Angelina Jolie’s story it is important to keep in mind that having either of these genes does not mean that a woman will develop either breast cancer or ovarian cancer. (2)

The BRCA genes play an important role in repairing the breaks or mutations in the DNA in our cells. But just as the body has a number of pathways that lead to cancer, it also has several pathways to repair DNA. The majority of women who are diagnosed with breast cancer have completely intact BRCA genes so there is obviously more to this than genomics.

It is also worth noting that men who inherit either of these genes may be at increased risk of prostate cancer as well as breast cancer – “breast cancer in men carrying BRCA2 has also been described in the medical literature.” (2)

Genetic Testing
The demand for genetic testing is probably also going through the roof as a result of the New York Times article. Yet, Professor Lindeman urges caution, and advises against routine genetic testing. “Testing is offered to people who have developed breast or ovarian cancer where there are features that might suggest a mutation is present,” he says.

The test is also extremely expensive as Myriad Genetics, a Utah-based company, patented the test and is currently the sole producer of it. In fact Myriad claims to own the rights to any test associated with the BRCA1 and BRCA2 genes and it has ruthlessly enforced that right, even though their test is inferior to one that Yale University was willing to provide at a much lower cost. The US Supreme Court has recently begun deliberations on the latest of a series of legal challenges to the granting of the patent that has been going on for over three years.

Referring to the fact that her wealth meant she has choices that other women do not have, Angelina Jolie observed that, “the cost of testing for BRCA1 and BRCA2, at more than $3,000 in the United States, remains an obstacle for many women.”

Overdiagnosis
Angelina Jolie’s situation also differs in other respects from those of the average woman. She is a woman at high risk compared to the vast majority of women who take part in breast screening programmes and after a biopsy receive a diagnosis of breast cancer. It is now known that about a quarter of cancers detected are so small or slow-growing that they will never metastasise or cause any health problems.

Other women are told they have ductal carcinoma in situ (DCIS), a kind of pre-cancer in which abnormal cells are found in the milk-producing ducts. Before screening programmes were introduced, DCIS was rare. Now they account for around 25% of new breast-cancer cases, and preventat-ive double mastectomies among women in this group have risen by 188% since the late 1990s. (3)  This despite the fact that between 50 – 80% of DCIS cases will not develop into invasive cancer. In the USA the impact of such diagnoses turns thousands of healthy women into “cancer survivors” every year, and fuels the culture of fear, adding to women’s already exaggerated sense of risk of getting breast cancer. (4) 

The results of a large study of breast cancer diagnoses over the past 30 years appeared in the New England Journal of Medicine at the end of 2012. It found that despite substantial increases in the number of cases of early-stage breast cancer detecting, screening mammography had only marginally reduced the rate at which women present with advanced cancer and that there is substantial overdiagnosis accounting for nearly a third of all newly diagnosed breast cancers. The study suggested that more than one million women may have been unnecessarily diagnosed and treated. (5)

Preventative options
Professor Lindeman suggested that there were a number of preventative options such as “close monitoring which includes MRI scans and mammograms starting at a suitable age,” and breast cancer prevention drugs such as Tamoxifen. As for mastectomy followed by breast reconstruction, he estimated that on average about 20% of women in Australia found to be carrying the BRCA1 and BRCA2 genes opt for this option. (2) 

Mastectomy
As the breast cancer survivor quoted earlier put it, “having a mastectomy … is a huge ordeal. And reconstruction, while it can look great, will never have sensation. Not ever again. So before removing her breasts, a woman … should understand her personal risk of future disease. She should know that many breast cancers are survivable, and that the disease is not necessarily a death sentence… Knowledge is power: before you remove a breast, be sure you are fully informed” (3) 

References
1. http://www.nytimes.com/2013/05/14/opinion/my-medical-choice.html?_r=0
2. http://theconversation.com/angelina-jolie-has-had-a-double-mastectomy-so-what-is-brca1-14227
3. http://6thfloor.blogs.nytimes.com/2013/05/15/reacting-to-angelina-jolies-breast-cancer-news/
4. http://www.nytimes.com/2013/04/28/magazine/our-feel-good-war-on-breast-cancer.html?pagewanted=all&_r=0
5. http://www.nejm.org/doi/full/10.1056/NEJMoa1206809

May 2013



THE CAUSES AND PREVENTION OF BREAST CANCER

On 4th March 2011 the University of Otago’s department of Preventative & Social Medicine celebrated 125 years Public Health Teaching and Research by hosting a symposium in Dunedin in honour of Professor Sir David Skegg. Lynda Williams attended the symposium and reports on the presentation given by Valerie Beral –

Dame Valerie Beral, Professor of Epidemiology and Director of the Cancer Epidemiology Unit at the University of Oxford since 1998, is known for her leadership of the Million Women Study. Since it started in 1997, the Million Women Study has recruited more than 1.3 million UK women over 50 years of age via the National Health Service (NHS) breast screening centres. An incredible one in four UK women in the target age group are participating, making it the largest such study in the world.

Much of Professor Beral’s research focuses on the role of reproductive, hormonal and infectious agents in cancer, and she leads major international collaborative studies on breast, ovarian and endometrial cancer.

In August 2003 Professor Valerie Beral’s group published the landmark results showing that taking Hormone Replacement Therapy (HRT) increases a woman’s risk of developing breast cancer, and that an estimated 20,000 UK women aged 50-64 years may have developed the disease between 1993 and 2003 due to their use of HRT. The use of oestrogen before or after menopause increases the risk of breast cancer.

The publication of these findings resulted in a dramatic drop in the use of HRT. Over the following few years several countries began reporting a decrease in their rates of breast cancer. Professor Beral reported to those attending the symposium that over a dozen countries have now recorded a significant drop in the incidence of breast cancer among their population. In a recent finding from the Million Women Study reported in January 2011 the team found that women starting hormone therapy at the time of menopause were at greater risk of breast cancer than those starting it later. (1)

The presentation in Dunedin focused on the major factors responsible for the rising rates of breast cancer throughout the world. She listed five major factors that influence the risk of women developing breast cancer:
• The age at which a woman has her first baby
• The number of babies a woman has, with each additional birth reduc-ing her risk of breast cancer by 5-10%
• The time between each birth
• Breastfeeding for many months – the longer a woman breastfeeds the lower her risk of breast cancer.
• Incomplete pregnancies (miscarriage or abortion) have no effect

Thus the more children a woman has, the younger she is when she begins having them, and the longer she breastfeeds them (eg one to two years) the greater the reduction in her risk of getting breast cancer. The protective effect of one full-term birth takes longer than 10 years to disappear.

According to Professor Beral the incidence of breast cancer in developed countries would be more than halved if women had similar childbearing patterns to women in developing countries – having a first baby in early adulthood, having 5 – 6 children and breastfeeding them for two years.

Professor Beral reported on studies undertaken on women in rural and urban Africa which revealed that when urban African women adopted the childbearing patterns of women in developed countries, their rates of breast cancer increased rapidly to match those of women in the developed world.

It is the short term exposure in early adulthood to the hormones oestrogen, progesterone and prolactin during a full-term pregnancy followed by a lengthy lactation period that provides life-long protection against breast cancer.

Incidence of breast cancer
In 2000 there were 1 million new cases of breast cancer.

In 2008 there were 1.4 million new cases of breast cancer.

In 2030 2 million new cases of breast cancer are expected.

Almost all the increase is in the developing countries as women from rural areas move to urban centres, have fewer children and start childbearing later.

The minor players
The other factors involved in the increasing rates of breast cancer are the age at the beginning of menstruation, the age at menopause, height, weight and the consumption of alcohol. Referring to the modifiable factors involved in the increase in the incidence of breast cancer in the UK, Professor Beral stated that the 50,000 new cases of breast cancer in the UK each year could be reduced to 40,000 if no women were obese and they drank no alcohol.

Genetic factors do not play a big part in the risk of breast cancer, as they need the impact of nutritional factors such as alcohol use and obesity before triggering any genetic factors that may then come into play, Professor Beral said.

Reference
1. http://jnci.oxfordjournals.org/content/103/4/NP.1.full

March 2011
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