Affiliations: Palo Alto, CA
Dr. Lillington is Clinical Professor of Medicine, and Dr. Sachs is Clinical Associate Professor of Medicine, Stanford University Medical Center.
Correspondence to: Glen A. Lillington, MD, 1020 Siskiyou Dr, Menlo Park, CA 94025-7014; email@example.com
The demonstration of statistical associations between
states or events naturally suggests that the congruity may be more than
coincidental. Possibilities include that the two (or more) states have
an underlying common cause, or that one event or state is affecting or
causing the other. Nonskeptical acceptance of the latter post
hoc, ergo propter hoc theorem may result in erroneous conclusions.
A notable example occurred early in the last century with the
statistical demonstration that individuals who contracted tuberculosis
appeared to have a lower subsequent incidence of bronchogenic
carcinoma. A well-known statistician of that era suggested that the
tuberculous infection somehow conferred some protection from neoplastic
change. An equally logical explanation, which initially eluded the
thinkers of that era, was that the tuberculous disease, for which there
was little effective therapy, carried with it a high mortality that
prevented many younger consumptives from reaching the age levels in
which pulmonary neoplasms have a significant incidence.
After the statistical association between smoking and bronchogenic
carcinoma was clearly demonstrated in the 1950s and 1960s, the howls of
denial from the tobacco industry were echoed faintly by disinterested,
honest statisticians exploring the possibilities that the association
might not be cause and effect. One such postulate, the Fisher
hypothesis, suggested a genetic predisposition toward smoking that
might also entail a predisposition toward developing bronchogenic
Critics pointed out that these studies were showing associations of
smoking not only with lung cancer and emphysema, but also with cancers
in other organs (such as the urinary bladder), and even with the
incidence of industrial accidents. It was postulated that the results
were almost “too good,” suggesting the presence of some
type of systematic statistical error, which might even call into
question the validity of the most robust association, that of smoking
and primary lung cancer.
We now realize that many inhaled carcinogens can be absorbed readily
through bronchial and alveolar walls and, thus, easily gain access to
extrapulmonary organs through the systemic circulation. Although the
rationale for increased industrial accidents in smokers is not so
clear-cut, it is not too difficult to postulate a few possible
explanations for the association.
The study by Murin and Inciardi in this issue of CHEST (see
page 1635) indicates an association between tobacco smoking and an
increased incidence of pulmonary metastases from primary breast
carcinoma. Although the association appears to be real, it needs to be
confirmed by further studies. A possible association of tobacco smoking
with the development of pulmonary metastases from other organs, such as
the kidney, also should be investigated.
It seems logical that the association may represent a cause-and-effect
relationship between inhaled tobacco smoke and the development of
pulmonary metastases. The mechanism, though, is not clearly definable.
One may postulate that inhaled carcinogens from tobacco smoke are
absorbed into the pulmonary circulation and then carried to the site of
the primary breast tumor to stimulate the release of tumor material
into the systemic veins or lymphatics. Conversely, the effect of the
circulating carcinogens from tobacco smoke may stimulate the growth of
occult metastases in the lungs. A third possibility is that the inhaled
carcinogens somehow affect or alter the pulmonary tissues to make them
more receptive to tumor embolization or lymphangitic spread.
This study, if confirmed by others, points to the desirability of
providing effective treatment for tobacco dependence for those women
who are still smoking at the time of breast carcinoma diagnosis. Proven
agents, such as bupropion sustained release (Zyban; Glaxo Wellcome;
Research Triangle Park, NC) and the nicotine patch are often
successful.1–2 In some instances, higher doses of nicotine
may be required, using multiple nicotine patches and/or nicotine nasal
sprays or inhalers.2–4 Such regimens, with individualized
doses and accurate monitoring, are safe and
Additionally, women who have stopped tobacco smoke exposure only within
the previous 12 months should be closely monitored for tobacco use,
since relapse back to tobacco use is greatest within the first 12
months after stopping smoking. Vigorous treatment for achieving smoking
cessation will probably become part of standard therapy in smokers with
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