Monday, March 24, 2014

The MAMMOGRAM Conundrum

To know is to know that you know nothing.That is the meaning of true knowledge - Socrates.

The recent Canadian study posed two questions for breast screening:

1.       Does mammography create over diagnoses?
2.       Does mammography as a screening tool help survival?

The answers gleaned from the study were “Yes” and “No.”

Now my two cents...

Let us look at some facts: The predicate of over diagnosis is based upon the argument that early diagnosis is an over diagnosis. In other words finding and treating a DCIS (Ductal carcinoma in situ) is an over diagnosis. Or so some will have you believe. They cite the SEER data and presume that some DCIS can regress back to normal states. Has anyone seen or documented a DCIS regression back to normal? The answer surprises us with a definitive No. Has anyone determined a DCIS by radiological means and then just followed the regression? The reverse answer however can be answered unequivocally that DCIS lesions have been noted to break through the basement membrane and run amok elsewhere in the body when left untreated over time. Studies in the past have estimated reduced mortality (0.3-3.2/1000 women). So if a woman’s life is saved that is a 100% save rate for that woman. Population data does not reflect the need of an individual. It only shows probabilities.

Another way to look at it is, knowing that 10% of all “abnormal” mammograms represent (true positive) cancer diagnosis and only 8-19% of the screened individuals have cancers detected as DCIS. That means over 80% of the cancers are invasive. Invasion indicates propensity to metastasize thus at least 8% of women will be diagnosed early and potentially saved.

Another remarkable non-statement in the study quotes a 5 year survival rate of 100% but fails to mention the 10 year survival rate for DCIS to be 98%. The 2 percent, loss due to breast cancer related mortality, seem not to fit the paradigm of limited disease in the paper.

So the question that we have to answer then is; does screening save lives? The NSABP-17 trial: Of the 818 women enrolled in the trial, 80% were diagnosed by mammography, and 70% of the patients' lesions were 1 cm or less. At the 12-year actuarial follow-up interval, the overall rate of in-breast tumor recurrence was reduced from 31.7% to 15.7% when radiation therapy was delivered (P< .005). Radiation therapy reduced the occurrence of invasive cancer from 16.8% to 7.7% (P = .001) and recurrent DCIS from 14.6% to 8.0% (P = .001). And the EORTC 10853 study: Similarly, of the 1,010 patients enrolled in the trial, mammography detected lesions in 71% of the women. At a median follow-up of 10.5 years, the overall rate of in-breast tumor recurrence was reduced from 26% to 15% (P < .001) with a similarly effective reduction of invasive (13% to 8%, P = .065) and noninvasive (14% to 7%, P = .001) recurrence rates

  The answer, if we are to follow the population based thinking comes from both cohort studies and randomized studies that show a decline in breast cancer related deaths since 1980s when mammography screening was mass utilized. After the initial significant decline post mass screening, the mortality rate from breast cancer has been steady. These trials were initiated between 1963 and 1982 the Health Insurance Plan study, the Malmo study, the Swedish Two county trial, the Edinburgh trial, the Stockholm trial, the Canadian National Breast Screening studies 1 & 2 and the Gothenburg Breast Screening Trial. All but the National Breast Cancer Screening found mammography to result in significant reductions in breast cancer mortality. . 

The NCI report and the SEER data show an incidence of DCIS has increased over time: 5.8/100,000 in 1975 vs. 32.5/100,000 in 2004 which is partly due to mammography yet remains meager to the 124.3/100,000 for invasive breast cancer. Most trials have shown reduced mortality from mammography. Does that mean we are over diagnosing? Or catching it early with a potential for cure? But even relenting a bit, the overall incidence of invasive breast cancer has declined since 1987 and especially since 2000 partly from the HRT knowledge and from catching the disease early. So, thinking this through further we find, a review commissioned by the AHRQ assessed the effectiveness of needle biopsy. The authors synthesized the evidence from 104 studies and concluded that 24% of tumors with DCIS identified from stereotactic guided automatic gun core needle biopsy were found to have found to have invasive breast cancer upon surgical excision (95% CI 0.18;0.32). Early diagnosis and removal therefore does have a decent payback.

What will happen another decade from now if the current professorial intuit plays out and makes women fearful of screening? Only time will tell.  The tragedy of more than 200,000 women being diagnosed with breast cancer and 40,000 dying from it annually in the United States is a reminder to all the well intentioned souls. 

The answers then might be answered as “No” and “Yes.”

Diagnosis and Management of Ductal Carcinoma in Situ (DCIS)Evidence Reports/Technology Assessments, No. 185.Virnig BA, Shamliyan T, Tuttle TM, et al. Rockville (MD): Agency for Healthcare Research and Quality (US); 2009 Sep.

Fisher ER, Dignam J, Tan-Chiu E, et al. Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of Protocol B-17: intraductal carcinoma. Cancer. 1999 Aug 1;86(3):429–38. 
Smith BD, Haffty BG, Buchholz TA, et al. Effectiveness of radiation therapy in older women with ductal carcinoma in situ. J Natl Cancer Inst. 2006 Sep 20;98(18):1302–10. 
Solin LJ, Fourquet A, Vicini FA, et al. Long-term outcome after breast-conservation treatment with radiation for mammographically detected ductal carcinoma in situ of the breast. Cancer. 2005 Mar 15;103(6):1137–46.

Nystrom L, Andersson I, Bjurstam N, et al. Long-term effects of mammography screening: updated overview of the Swedish randomised trials. Lancet. 2002 Mar 16;359(9310):909–19

Roberts MM, Alexander FE, Anderson TJ, et al. The Edinburgh randomised trial of screening for breast cancer: description of method. Br J Cancer. 1984 Jul;50(1):1–6.

Frisell J, Lidbrink E, Hellstrom L, et al. Followup after 11 years--update of mortality results in the Stockholm mammographic screening trial. Breast Cancer Res Treat. 1997 Sep;45(3):263–70.

Miller AB, To T, Baines CJ, et al. Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50–59 years. J Natl Cancer Inst. 2000 Sep 20;92(18):1490–9.

Miller AB, To T, Baines CJ, et al. The Canadian National Breast Screening Study-1: breast cancer mortality after 11 to 16 years of follow-up. A randomized screening trial of mammography in women age 40 to 49 years. Ann Intern Med. 2002 Sep 3;137(5 Part 1):305–12.

Bjurstam N, Bjorneld L, Warwick J, et al. The Gothenburg Breast Screening Trial. Cancer. 2003 May 15;97(10):2387–96.

Shapiro S. Periodic screening for breast cancer: the HIP Randomized Controlled Trial. Health Insurance Plan J Natl Cancer Inst Monogr. 1997:27–30.

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