In a five-part series, the Herald investigates controversies in cancer testing and treatment and reports on the moving stories of people afflicted with cancer. In the first part of the series, Herald health reporter Martin Johnston turns his attention to breast cancer

New Zealand's breast cancer death rate dropped by 20 per cent in the decade after the start of the national breast screening programme.

Yet we remain well above Australia and we are in the one-third of OECD nations with the highest rates.

Breast cancer is the most commonly registered cancer in New Zealand women, with around 3000 cases a year. And it was the third most common cancer killer in 2012 for women, with 617 deaths.

The years since 1999, when free two-yearly mammograms were first offered to women aged 50 to 64, have been marked by great improvements in the medicines to treat breast cancer, but prices have escalated ahead of the Government's willingness to pay, and now the screening programme is facing challenges.

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In 2004 the Government extended the upper screening age to 69 and, after lobbying from cancer charities, reduced the entry age to 45.

"The evidence hasn't been strong enough for us to be screening women aged 45 to 49," says Associate Professor Brian Cox, a cancer epidemiologist at Otago University. "The effects of reducing breast cancer mortality seems to be much less than with screening older women.

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"There are issues in terms of the numbers of false positives and the whole issue of excess detection or over-diagnosis of younger women. It creates a debate that may put older women off from participating."

In June, experts at the World Health Organisation's cancer research agency said the evidence for screening women aged 40 to 49 only was "limited".

But for the 45-49 sub-group, this sceptical view was carried on a slim majority vote, the rest believing the evidence was "sufficient".

In July, British researchers reporting their study of women aged 40 to 49 said annual screening was associated with a lower breast cancer death rate.

But Professor Ann Richardson, cancer epidemiologist at Canterbury University, says those results are puzzling.

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"Most groups who formally review screening have tended to recommend screening for women over 50 but not for women under 50."

She says this is because breast cancer is less common before 50; older-style mammogram screening x-rays don't perform as well in younger women because of typically denser breasts (although that may be changing with the move to digital mammogram machines); and there is a greater chance of false positives in the younger group.

We sit down with Tracey Eising who tells of the breast cancer that has been with her for nine years and how without state funding she can’t afford the one remaining medicines that could help her once her current drugs fail.

The Breast Cancer Foundation urges women to have mammograms from 40, for which they must pay around $160 themselves or rely on insurance until they reach 45. It argues the benefits outweigh risks such as false positives.

Dr Reena Ramsaroop, a pathologist and chair of the foundation's medical advisory committee, says she thinks 50 should be the lower age and that screening younger women is not cost-effective. But she does suggest extending the maximum age to 74 - Australia's upper limit - partly because research at the Auckland Breast Cancer Register found that 11 per cent of patients were aged over 70 and around half had higher-grade tumours.

The clinical leader of the Government screening programme, Dr Marli Gregory, says: "In the New Zealand context it may be the correct decision to screen from 45 because our Maori women, who we have always known had a higher rate of breast cancer and poor outcomes, have the same incidence of breast cancer in that age group as other women do in the country aged over 50."

Tumours that matter

Screening healthy women has been associated with a big increase in the detection of ductal carcinoma in-situ (DCIS), which hasn't spread outside the milk ducts of the breast.
It accounts for about 21 per cent of all NZ screening-programme diagnoses in women aged 50-69 and 29 per cent in the 45 to 49-year-olds. "Ductal carcinoma in-situ is not cancer and treating it as such is ridiculous," says Lynda Williams, co-ordinator of the Auckland Women's Health Council.

"Clusters of abnormal cells like DCIS can disappear, stop growing or simply remain but never cause a problem. Abnormal cells may therefore not require treatment.

"Calling it cancer is misleading, frightening and likely to get compliance to mastectomy or lumpectomy from women without giving them the options of watch and wait. Being watched and having a regular screen is one of the options for DCIS in the earlier stages."
She points to American findings that the breast-cancer death rate for women initially diagnosed with DCIS was little higher than the lifetime risk of dying from the disease among all women.

"For the lowest-risk lesions, observation and prevention interventions alone should be tested. Diet, exercise, moderate alcohol intake, and avoidance of postmenopausal hormone therapy with progesterone-containing regimens should be the starting point for prevention," experts said in the oncology journal of the American Medical Association.
"High-risk lesions - eg HER2 positive, patient age less than 40 years, hormone receptor negative, large size - are lesions that should still be aggressively treated."

Dr Ramsaroop said DCIS is mainly detected from mammogram findings of tiny calcium deposits. A radiologist can identify them as benign, malignant or indeterminate. It is usually the indeterminate ones that are biopsied, allowing the pathologist to diagnose them as benign or DCIS/malignant.

DCIS can be divided into low, intermediate or high grade. The high-grade cells are the most likely to progress to invasive cancer, but the low and intermediate ones can too.
Professor Richardson notes there is still a poor understanding of how DCIS behaves if not treated.

"There does seem to be more evidence accumulating now that for low-grade DCIS it may be sufficient to leave it. There's going to be a trial to look at that overseas [comparing a surgery group with annual screening]."

Drugs

Soon after winning office in 2008, John Key's Government enacted its election promise to instruct health authorities to expand funding of Roche's Herceptin. But now, in its third term, it is leaving the breast cancer decisions to Pharmac.

The Breast Cancer Aotearoa Coalition, which led an assertive and emotional Herceptin campaign in 2008, is pushing for Pharmac to fund Perjeta and Kadcyla, two pricey new Herceptin follow-ups from Roche for women with certain kinds of advanced breast cancer and whose tumours have tested as susceptible to Herceptin.

Kadcyla's trick is that once its Herceptin component has attached to its target protein on the tumour cell surface, it delivers a payload chemotherapy to inside the cell. In trials this two-part medicine extended women's lives by a median of 5.8 months more than standard treatment did.

Perjeta's addition to patients' median overall survival - when taken with the standard regimen of Herceptin and chemotherapy - was even greater, at around one year and four months, when compared to the standard therapy.

Both drugs are state-funded in Australia and the coalition says: "Any lag in funding [Perjeta] here will increase the transtasman differences in breast cancer mortality."
"A lot of women look over there and see they are getting the drugs and wonder why we can't," says deputy chairwoman Chris Walsh.

When Roche requested funding of Perjeta, a Pharmac committee supported the bid but said the drug was very expensive and assigned it low priority - the kiss of death unless Roche radically cuts the price.

Roche hasn't applied for funding of Kadcyla because the standard treatment it would be compared with in New Zealand is a cheap generic, making it harder to show cost-effectiveness.

The company offers the two drugs to women at a discount on its international price by not charging for a number of treatment cycles, but they are still costly. The capped prices are $70,719 for Perjeta and $82,878 for Kadcyla, although these are just for the drugs and exclude GST and clinic costs. If a woman starts on Perjeta and progresses to Kadcyla, the total capped drug cost is $100,000.

While some health insurers' policies will contribute towards drugs not funded by Pharmac, as long as they are Medsafe registered, few would cover Perjeta or Kadcyla for more than several months.

Roche NZ general manager Dr Lance Baldo says few women have joined the company's Perjeta or Kadcyla "access" programmes, possibly partly because the Auckland City Hospital Cancer Centre at first wouldn't pay for Herceptin if a woman was receiving Perjeta.

But the hospital's head of cancer care, Dr Richard Sullivan, says it dropped its objection earlier this year to women splitting their care between free public-sector Herceptin and private-sector Perjeta, which had arisen from the clinical risks of divided care.

"We have developed a shared-care model. I'm not aware of anyone who did have to pay [for Herceptin] but we did have a policy and that might have prevented people from asking."

Research

In Christchurch, some women booked in for breast cancer surgery are taking part in a trial to see if taking aspirin might enhance the effectiveness of drugs that block production of the hormone oestrogen.

Plain, cheap, anti-inflammatory aspirin has become a new focus of cancer research after it was noticed in trials of the drug for preventing cardiovascular disease that patients taking it had a lower risk of several types of cancer. But because cancer wasn't the focus of the studies, more-specific trials are needed.

"It's all suggestive," says Otago University scientist Dr Anita Dunbier. She is involved in the Christchurch study of women with hormone-receptor positive breast cancer. Samples of their tumours are taken two weeks before, and at surgery to see if adding aspirin to aromatase-inhibitor drugs affects gene expression.

She says a high level of inflammation in an oestrogen-receptor-positive tumour before treatment is associated with a poor response to aromatase inhibitors.

"[Our] work in patients and in-vitro suggests we can improve effectiveness by reducing that level of inflammation."

Personalised medicine

Herceptin is among a growing number of personalised cancer drugs. It is only given to women whose tumours are found by lab tests to be producing excessive amounts of the HER2 receptor protein.

Another line of Dr Dunbier's research is evaluating new genetic tumour tests that it is hoped can be used to tailor treatment.

One, Oncotype DX, may be useful for women with early-stage cancer which is oestrogen-receptor positive and Her-2 negative. It has been approved by the National Institute for Health and Care Excellence in the UK, which also concluded the evidence for three other tests it studied was less conclusive.

Oncotype DX testing costs about $5000 and groups women into those of low risk of cancer recurrence and likelihood to benefit from chemotherapy, intermediate risk and high risk. It can help in deciding whether chemotherapy is worth the risk of unpleasant and harmful side effects.

Widely used in the US, it is not provided within New Zealand, but is offered to New Zealand patients from an Australian website.

Dr Dunbier says this test and another are funded by US insurance companies and are seen as the best standard of care, "but they also save them a lot of money if women aren't going to benefit [from chemotherapy]."

But Palmerston North cancer specialist Dr Richard Isaacs, although excited by the future possibilities of such tests, believes there is a way to go.

"Many groups are producing limited gene expression tests to try to help us choose which patients should have each treatment. The trouble is, the tests don't correlate well [with each other] cost thousands and are not readily available here or in Australia."

The Series

Today:

Breast cancer

Tomorrow:

Bowel cancer

Wednesday:

Lung cancer

Thursday:

Melanoma

Friday:

Prostate cancer