"Cure" for Invasive Breast Cancer Elusive in 1980s and 1990s

Nick Mulcahy

September 21, 2009

September 21, 2009 — A "cure" for invasive breast cancer — that is, a mortality rate among women with the disease that is the same as their counterparts in the general population — was not attained in the 1980s and 1990s, according to a new study published in the Annals of Oncology.

However, for a variety of reasons, a number of breast cancer experts questioned the value of the study.

The study looked women in parts of England and Australia who were diagnosed with invasive breast cancer from 1980 to 1995. The women had a continuous excess mortality attributable to their disease for up to 23 years after diagnosis, the investigators found.

We have not yet seen the long-term impact of newer drugs.

The study did not examine women by detection method or by type of treatment received, which could have yielded different results by subgroups, the investigators acknowledge.

Also, the time period of the study makes the conclusion open to possible revision, suggests an editorial accompanying the study.

"We have not yet seen the long-term impact of newer drugs like taxanes; targeted therapies like trastuzumab, lapatinib, aromatase inhibitors, extended hormonal treatment, bisphosphonates; and use of tumor genomics on survival of breast cancer," write the editorialists, M. K. Singhal, MD, and Vinod Raina, MD, from the All India Institute of Medical Sciences in New Dehli.

Cure Definable at Population Level

Clinical cure for an individual is never certain, but cure is an idea definable at a population level, explain the study authors, headed by Laura M. Woods, PhD, from the Cancer Research UK Survival Group at the London School of Hygiene and Tropical Medicine in the United Kingdom. They write: "The 'cured' subpopulation is the proportion of patients among whom no additional, or 'excess', mortality is observed compared with the population from which they are drawn."

Population cure is obtained when the excess mortality rate reaches 0, they add.

The literature on breast cancer cure is inconsistent, with some studies having found that excess mortality levels reach the status of cure after about 20 years, note both the study authors and the editorialists. However, cure has been limited to subgroups, say the study authors.

Subgroups are what really matters, suggested an American breast cancer expert approached by Medscape Oncology.

Most clinicians and researchers consider breast cancer a group of diseases rather than 1 disease.

"Using data that do not account for disease heterogeneity will reduce its applicability and general acceptance by clinicians," said Kim Hirshfield, MD, assistant professor of medicine at the University of Medicine and Dentistry, New Jersey in New Brunswick. She pointed out that the new study looks at a broad swath of breast cancer patients with no breakdown by molecular and histologic subtype or disease stage. "Most clinicians and researchers consider breast cancer a group of diseases rather than 1 disease," she added.

Dr. Hirshfield also said that "population-based cure is not a concept that is discussed as part of our medical training," and that, in general, clinicians do not think of cure in that way.

An Exception: Older Women Cured

In the study, the authors studied populations (in West Midlands, United Kingdom and New South Wales, Australia) that were diagnosed with invasive breast carcinoma from 1980 to 1995 and followed-up until 2002.

The authors compared the observed death rates in the study population with the expected mortality for women in the respective background populations, using the annual age-group-specific death rates for each region.

Excess mortality was more than 0 for all breast cancer disease groups (localized, regional, distant, and unstaged) in both populations and for all women diagnosed before age 65. The problem was also continuous; the excess mortality was more than 0 at 10, 15, and even 23 years after initial diagnosis.

In short, there was no cure in either the British or Australian population.

However, subsets of patients older than 65 years in New South Wales and older than 70 years in West Midlands were considered cured.

Some Words About Screening and Treatment Advances

The study authors contend that women in the study would have benefited from "recent advances in treatment, particularly during the 1980s." They also note that a "large proportion of women aged 50 to 69 years" diagnosed from 1988 to 1995 would have been screen detected because screening programs were in place in each locale at that time.

This leads the authors to conclude that the 2 phenomena, treatment advances and screening, have not led to a cure.

The editorialists question that idea by noting that there is an array of recent advances (such as trastuzumab and aromatase inhibitors) that many women in the study would not have had long-term exposure to. In other words, the jury may still be out on whether or not treatment advances have moved breast cancer in general toward a cure (population-based definition), say the editorialists.

The study authors conclude their paper by saying that an analysis of cure by detection method and type of treatment would help in understanding if the apparent lack of cure continues to apply to young and middle-aged breast cancer patients.

The researchers have disclosed no relevant financial relationships.

Ann Oncol. 2009; 20:1291-1292 and 1331-1336. Abstract, Abstract

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