Steven Narod, MD, FRCPC
In a recent issue of The New York Times, Barron Lerner discussed Betty Ford’s breast cancer diagnosis in 1974.1 He described the state of the art of breast cancer treatment at the time and how her diagnosis accelerated the uptake of screening across the country. But her cancer was not screen-detected, and it was node-positive. He suggested, rather, that her cancer was cured by chemotherapy: “Mrs. Ford probably survived her cancer (she died in 2011 at age 93) because she received an early version of chemotherapy.”
It is timely to consider how our understanding of breast cancer screening and treatment has evolved in the 50 years that have passed since Betty Ford was diagnosed and why the conventional view of cancer progression needs to be revisited.
Underlying Premises
The purpose of breast screening is to identify breast cancers when they are small and node-negative, hoping we can intercept them before they become life-threatening. This is based on the observation that the larger the cancer, the more likely it is to prove fatal. The premise here is that as cancers enlarge, they tend to spread to the lymph nodes and distant organs, such as the lungs, liver, and bone. This is not entirely true; it may come as a surprise to many that women with cancers that are 1 cm have the same survival rate as women with cancers that are 1 mm, even though they contain 1,000 times more cells.2
Betty Ford’s cancer was lymph node–positive. No one suggests that mammographic screening is intended to find lymph node–positive cancers, even though the size/survival relationship is more profound for women with lymph node–positive cancers than for women with lymph node–negative cancers.3 In our patient database at Women’s College Hospital, a decline of 1.0 cm was associated with a reduction in 15-year mortality of 2.5% in the node-negative group and 10.3% in the node-positive group. Does this imply that finding node-positive cancers is a benefit of mammography?
The landmark study of the past 50 years was Bernie Fisher’s National Surgical Adjuvant Breast and Bowel Project study. It showed that women with breast cancer fared equally well whether they had a lumpectomy or a radical mastectomy, even though the mastectomy group experienced far fewer breast cancer recurrences than the lumpectomy group, and experiencing a local recurrence increased the mortality rate.4 The addition of radiotherapy reduces the recurrence rate but not the death rate. This was known to us in 1991.
Thirty years on, we showed that women who develop a new cancer in the opposite breast have a fourfold increase in the risk of dying of breast cancer thereafter. But preventing the second breast cancer via bilateral mastectomy does not reduce the risk of death.5
Ductal carcinoma in situ (DCIS) is considered a precursor to invasive cancer but not a cancer in its own right. About 20% of women with DCIS treated with lumpectomy alone will later develop an invasive cancer in the same breast. The recurrent cancers are generally considered to be a potential source of metastases—after experiencing a local invasive recurrence, the 20 year mortality rises from 2% to 16%.6 Invasive recurrences are rare after mastectomy. But in a paper published in JAMA Oncology (and also featured in The New York Times), we have shown that women treated for DCIS have the same survival rate (97%) whether they are treated with lumpectomy or with mastectomy.7 This implies that the local invasive recurrence after DCIS is not the source of metastases. If it were, then preventing the invasive cancer by mastectomy would be life-saving, but it is not.
Conventional Wisdom Reconsidered
In each of the three scenarios previously discussed, it is shown that preventing an invasive cancer through more extensive surgery does not prevent death. If preventing cancer does not save lives, why should early detection be better?
In 2014, I was the senior author on the Canadian National Breast Screening study.8 We randomly assigned nearly 90,000 women aged 40 to 59 to receive either five yearly mammograms or a physical examination. After 30 years, the number of deaths from breast cancer was almost the same in both groups.
Our study was widely criticized by the radiology community, despite it being named one of the five top papers of the decade in the British Medical Journal. The critics claimed we engaged in faulty randomization—that is, we shunted women with palpable breast masses to the mammography arm and thereby inflated the number of women with cancer in the screened group.
The facts tell us otherwise. At the first round of screening, there were 174 palpable cancers in the screened group (of whom 54 died of breast cancer), and there were 170 palpable cancers in the unscreened group (of whom 47 died of breast cancer). Moreover, I reanalyzed the data after removing all the women who were diagnosed with cancer at the first round, and the results were the same—again no benefit. No one cites our paper in the movement to expand mammographic screening across North America—but I stand by it.
Data in Context
Much of the decline in the mortality rate of breast cancer in the United States since the 1970s can be attributed to more widespread use of chemotherapy. Chemotherapy reduces the death rate by about one-third. For a 56-year-old woman with one or two positive nodes, such as Betty Ford, chemotherapy cuts the mortality rate from about 30% to 20%. So, about 1 in 10 patients is “cured” by chemotherapy—but without chemotherapy, about 7 in 10 are “cured.” It surprised me to learn that the majority of women whose cancer has already spread to the lymph nodes will be cured with local surgery alone. Reiter et al suggest that this is because the lymph node metastases and the distant metastases have separate origins.9
It is reassuring that the majority of women diagnosed with breast cancer in the United States today will not develop progression to metastatic breast cancer, even without chemotherapy. I think this says much about the insidious nature of breast cancer. Going forward, I think it should be a priority for researchers to focus on what the earliest stages of breast cancer are and to identify the source of the rogue cells that do lead to distant spread—and strive to eliminate them. Looking for small cancers with a mammogram may be beneficial for some, but that will not get us to where we want to be.
DISCLOSURE: Dr. Narod reported no conflicts of interest.
REFERENCES
1. Lerner BH: The complicated legacy of Betty Ford’s breast cancer story. The New York Times. October 3, 2024.
2. Sopik V, Narod SA: The relationship between tumour size, nodal status and distant metastases: on the origins of breast cancer. Breast Cancer Res Treat 170:647-656, 2018.
3. Narod SA: Tumour size predicts long-term survival among women with lymph node-positive breast cancer. Curr Oncol 19:249-253, 2012.
4. Fisher B, Anderson S, Bryant J, et al: Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347:1233-1241, 2002.
5. Giannakeas V, Lim DW, Narod SA: Bilateral mastectomy and breast cancer mortality. JAMA Oncol 10:1228-1236, 2024.
6. Sopik V, Iqbal J, Sun P, et al: Impact of a prior diagnosis of DCIS on survival from invasive breast cancer. Breast Cancer Res Treat 158:385-393, 2016.
7. Narod SA, Iqbal J, Giannakeas V, et al: Breast cancer mortality after a diagnosis of ductal carcinoma in situ. JAMA Oncol 1:888-896, 2015.
8. Miller AB, Wall C, Baines CJ, et al: Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: Randomised screening trial. BMJ 348:g366, 2014.
9. Reiter JG, Hung WT, Lee IH, et al: Lymph node metastases develop through a wider evolutionary bottleneck than distant metastases. Nat Genet 52: 692-700, 2020.
Dr. Narod is Professor of Epidemiology at the University of Toronto. He held the Canada Research Chair in Breast Cancer for 21 years. He is the author of A Fair Trial: The Foundations of Breast Cancer. In 2024, he was elected to the Canadian Medical Hall of Fame.
