Royce v. Wyeth et al
Filing
393
MEMORANDUM OPINION AND ORDER denying defendants' 205 MOTION to Exclude the testimony of Dr. Michael Wertheimer; and denying plaintiff's 253 MOTION to Exclude expert testimony that combination hormone therapy does not generally cause breast cancer. Signed by Judge John T. Copenhaver, Jr. on 7/8/2011. (cc: attys) (taq)
UNITED STATES DISTRICT COURT
SOUTHERN DISTRICT OF WEST VIRGINIA
AT CHARLESTON
LEAH ROYCE HINES,
Plaintiff,
v.
Civil Action No. 2:04-0690
WYETH, d/b/a Wyeth, Inc.;
WYETH PHARMACEUTICALS, INC.;
and PHARMACIA & UPJOHN COMPANY,
Defendants.
MEMORANDUM OPINION AND ORDER
Pending is defendants’ motion to exclude the expert
testimony of Dr. Michael Wertheimer (Doc. No. 205), filed May 27,
2011.
Pending as well is plaintiff’s motion to exclude expert
testimony from Drs. Chodosh, Meile, and Levy that combination
hormone therapy does not generally cause breast cancer (Doc. No.
253), also filed May 27, 2011.1
1
At a pretrial conference on June 17, 2011, the court
conferred with counsel regarding the necessity of an evidentiary
hearing on the various Daubert motions currently pending before
the court. (See Doc. No. 343). The parties made clear that such
a hearing was not necessary. Defendants have, however, requested
oral argument on the motions. Inasmuch as the parties’ briefs
and supporting exhibits adequately present the issues ripe for
adjudication, the court finds that oral argument would not aid
the decisional process and accordingly denies defendants’ request
for oral argument as to the motions discussed herein.
I.
This is a pharmaceutical products liability action in
which plaintiff Leah Royce Hines alleges that she developed
breast cancer as a result of ingesting hormone replacement
therapy (“HRT”) drugs manufactured by defendants.
HRT here
consists of two medications, estrogen and progestin (“E+P”), that
are commonly prescribed in combination to treat menopausal
symptoms.
This action concerns three HRT drugs: Premarin,
Prempro, and Provera.
Defendant Wyeth, LLC (“Wyeth”)
manufactured Premarin, an estrogen drug, and Prempro, a
combination estrogen and progestin drug.
Defendant Pharmacia &
Upjohn Company (“Upjohn”) manufactured and distributed Provera, a
progestin drug.
The generic name for Provera is
medroxyprogesterone acetate (“MPA”).
Plaintiff’s physician prescribed HRT drugs to treat her
menopausal symptoms from approximately July 1994 to April 1999.
She was diagnosed with breast cancer in July 1999, and thereafter
instituted this action on July 7, 2004, invoking the court’s
2
diversity jurisdiction.2
Her complaint asserts claims against
defendants for negligence, strict liability (design defect and
failure to warn), and breach of implied warranty.
Defendants seek to exclude the testimony of plaintiff’s
specific causation expert, Dr. Michael Wertheimer.
Plaintiff has
moved to exclude expert testimony from Drs. Chodosh, Meile, and
Levy that combination hormone therapy does not generally cause
breast cancer.
II.
The admission of expert testimony is governed by
Federal Rule of Evidence 702 and the Supreme Court’s decision in
Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579
(1993).
Under Rule 702 and Daubert, expert testimony must
satisfy a two-prong test: (1) the testimony must concern
“scientific, technical, or other specialized knowledge”; and (2)
it must “aid the jury or other trier of fact to understand or
resolve a fact at issue.”
Westberry v. Gislaved Gummi AB, 178
F.3d 257, 260 (4th Cir. 1999) (citing Daubert, 509 U.S. at 592);
2
The case was transferred to multidistrict litigation in
the United States District Court for the Eastern District of
Arkansas on October 26, 2004. Over five years later, on April
13, 2010, it was remanded to this court for the completion of
discovery, pretrial activity, and trial.
3
Fed. R. Evid. 702.
“The first prong of this inquiry necessitates
an examination of whether the reasoning or methodology underlying
the expert’s proffered opinion is reliable -- that is, whether it
is supported by adequate validation to render it trustworthy.”
Westberry, 178 F.3d at 260.
“The second prong of the inquiry
requires an analysis of whether the opinion is relevant to the
facts at issue.”
Id.
Thus, an expert’s testimony is admissible
under Rule 702 if it “rests on a reliable foundation and is
relevant.”
Kumho Tire Co. v. Carmichael, 526 U.S. 137, 141
(1999).
As to the reliability prong, the Court in Daubert
announced a non-exhaustive list of factors to guide the trial
judge’s inquiry, including “(1) whether a theory or technique can
be or has been tested; (2) whether it has been subjected to peer
review and publication; (3) whether a technique has a high known
or potential rate of error and whether there are standards
controlling its operation; and (4) whether the theory or
technique enjoys general acceptance within a relevant scientific
community.”
Cooper v. Smith & Nephew, Inc., 259 F.3d 194, 199
(4th Cir. 2001) (citing Daubert, 509 U.S. at 592-94).
As to the relevancy prong, “the expert’s proffered
scientific testimony must be sufficiently tied to the facts of
4
the case that it will be of assistance to the factfinder in
resolving a disputed fact.”
Bourne ex rel. Bourne v. E.I. Dupont
de Nemours & Co., 189 F. Supp. 2d 482, 495 (S.D. W. Va. 2002).
“That is, there must be a ‘valid scientific connection to the
pertinent inquiry’ before the testimony is admissible.”
Id.
(quoting Daubert, 509 U.S. at 591-92).
Our court of appeals has summarized the overarching
duties of a trial court in resolving Daubert motions as follows:
A district court considering the admissibility of expert
testimony exercises a gate keeping function to assess
whether the proffered evidence is sufficiently reliable
and relevant . . . The inquiry to be undertaken by the
district court is “a flexible one” focusing on the
“principles and methodology” employed by the expert, not
on the conclusions reached. Daubert, 509 U.S. at 594-95
. . . In making its initial determination of whether
proffered testimony is sufficiently reliable, the court
has broad latitude to consider whatever factors bearing
on validity that the court finds to be useful . . . The
court, however, should be conscious of two guiding, and
sometimes competing, principles. On the one hand, the
court should be mindful that Rule 702 was intended to
liberalize the introduction of relevant expert evidence.
. . . [T]he court need not determine that the expert
testimony a litigant seeks to offer into evidence is
irrefutable or certainly correct . . . As with all other
admissible evidence, expert testimony is subject to being
tested by “[v]igorous cross-examination, presentation of
contrary evidence, and careful instruction on the burden
of proof.” Daubert, 509 U.S. at 596 . . . On the other
hand, the court must recognize that due to the difficulty
of evaluating their testimony, expert witnesses have the
potential to “be both powerful and quite misleading.”
Id. at 595 . . . [G]iven the potential persuasiveness of
expert testimony, proffered evidence that has a greater
potential to mislead than to enlighten should be
excluded.
5
Westberry, 178 F.3d at 261 (some citations and footnotes
omitted).
Ultimately, “[t]he proponent of the [expert] testimony
must establish its admissibility by a preponderance of proof.”
Cooper, 259 F.3d at 199.
III.
A.
Motion to Exclude Dr. Wertheimer’s Testimony
Background
Dr. Wertheimer is a board certified surgeon who
specializes in breast cancer.
Plaintiff seeks to introduce his
testimony to show that defendants’ HRT drugs caused her breast
cancer (i.e., specific causation).
His expert report provides
the following summary of his conclusions:
1.
E+P can cause and has caused hormone dependent
breast cancer in women.
The best estimate [based on
epidemiological studies] is that E+P has caused in excess
of 200,000 breast cancers in this country alone.
2.
The mechanism by which E+P causes breast cancer is
by promotion, which refers to the stimulation or fueling
of hormone dependent cells, lesions, and/or tumors so
that these pre-malignant and preclinical abnormalities
develop into clinical cancer.
3.
Once breast cancer is present, E+P acts to further
fuel the growth and development of the cancer by causing
the cells to continue to proliferate and divide thus
allowing for additional mutations and as such E+P causes
an aggravation of the woman’s pre-existing breast cancer
disease.
4.
I have used the methodology of differential
diagnosis or causality assessment as well as the
available epidemiological experimental and clinical
6
evidence to evaluate the cause of Mrs. Hines’s breast
cancer. In my opinion, Mrs. Hines’s use of E+P was a
substantial contributing factor and a factual and legal
cause of the development and growth of her breast cancer
so that, but for her use of E+P, she would not have
developed such cancer.
(Pl.’s Opp., Ex. 2, Wertheimer Report (“Wertheimer Rep.”) at 3).
Regarding case-specific opinions, Dr. Wertheimer’s
report notes that a pathological examination of plaintiff’s tumor
revealed that her breast cancer was estrogen receptor and
progesterone receptor positive (“ER/PR positive”).
(Wertheimer
Rep. at 13; Pl.’s Opp., Ex. 5, LRoyce-HKB&TSAI- 000 295-296).
He
observes that breast cancer that has positive estrogen or
progesterone receptors is known as “hormone dependent,” meaning
that the cancer requires hormones to develop.
at 13).
(Wertheimer Rep.
Dr. Wertheimer opines that there are two possible
sources of hormones necessary to develop hormone dependent
cancer: endogenous hormones (i.e., estrogen and progesterone
naturally produced by the body) and exogenous hormones (i.e.,
pharmaceutical hormones such as E+P).
(Id.).
Because
plaintiff’s medical history shows that her menopausal symptoms
improved on HRT drugs and returned to some degree after she
stopped taking the drugs, Dr. Wertheimer found that plaintiff was
a “low [endogenous] hormone producing” woman.
(Id. at 15).
Given her lack of naturally produced hormones, he concluded that
7
exogenous hormones, in the form of defendants’ HRT drugs, were
the likely cause of plaintiff’s ER/PR positive breast cancer.
(Id.).
In reaching this conclusion, Dr. Wertheimer addressed
other potential causes such as breast density, family history of
breast cancer, and exposure to ionized radiation, but ultimately
found that none of these factors posed a significant risk of
breast cancer for this particular plaintiff.
(Id. at 17).
Defendants move to exclude Dr. Wertheimer’s testimony
on the following grounds: (1) differential diagnosis is not a
reliable or generally accepted method of determining the cause of
an individual’s breast cancer; (2) Dr. Wertheimer has not tested
his theory that women who experience menopausal symptoms have a
low baseline level of endogenous estrogen (“natural estrogen”)
and are therefore at a low risk of breast cancer unless they take
HRT drugs, and studies by independent investigators contradict
this theory; and (3) even if differential diagnosis could be used
here, Dr. Wertheimer failed to conduct a proper differential
diagnosis because he did not rule out as causes of plaintiff’s
breast cancer her natural estrogen or her other risk factors for
breast cancer.
The court considers these contentions in turn.
8
B.
Use of Differential Diagnosis to Determine the Cause of
an Individual’s Breast Cancer
As the Fourth Circuit has explained, differential
diagnosis “is a standard scientific technique of identifying the
cause of a medical problem . . . by determining the possible
causes for the patient’s symptoms and then eliminating each of
these potential causes until reaching one that cannot be ruled
out or determining which of those that cannot be excluded is the
most likely.”
Westberry, 178 F.3d at 262.
It is typically
performed “after physical examinations, the taking of medical
histories, and the review of clinical tests, including laboratory
tests.”
Id. (internal citations omitted).
“A reliable
differential diagnosis provides a valid foundation for an expert
opinion under Rule 702.”
Cooper, 259 F.3d at 200 (emphasis in
original).
To be clear, defendants do not dispute that a reliable
differential diagnosis satisfies the Daubert standard.
They
instead claim that the use of differential diagnosis to determine
the cause of breast cancer is “inherently unreliable” because the
causes of breast cancer are unknown; there is no reliable means
for determining the cause of someone’s breast cancer; and
differential diagnosis is not a “generally accepted methodology”
in the breast cancer community.
9
The court is not persuaded by defendants’ contention
that the causes of breast cancer are categorically “unknown.”
Dr. Wertheimer cites various peer-reviewed articles and
epidemiological studies concluding that E+P causes breast cancer
in women.
(Wertheimer Rep. at 7 n.17 (citing, among others,
Colditz, Decline in Breast Cancer Incidence Due to Removal of
Promoter: Combination Estrogen Plus Progestin, 9 Breast Cancer
Research 108 (2007); MacMahon, Epidemiology and the Causes of
Breast Cancer, 118 Int. J. Cancer 2373-78 (2006); Fournier, Use
of Different Postmenopausal Hormone Therapies and Risk of
Histology- and Hormone Receptor-Defined Invasive Breast Cancer,
26(8) J. Clinical Oncology 1260-68 (2008); Katalinic, Trends in
Hormone Therapy and Breast Cancer Incidence -- Results from the
German Network of Cancer Registries, 76 Pathobiology 90 (2009))).
He also relies on the MacMahon article (cited above) to show that
there are “three known causes of human breast cancer: ionizing
radiation, beverage alcohol, and exogenous ovarian hormones
[i.e., E+P],” and notes that this view is “supported by every
major national and international scientific organization such as
the NCI [National Cancer Institute], ACS [American Cancer
Society], IARC [International Agency for Research on Cancer],
World Health Organization, and most leading scientists and
academicians in the field.”
(Id. at 17).
10
Defendants do not
challenge or even address these findings.3
While all causes of the disease are not known, the
medical literature shows that at least some potential causes of
breast cancer have been identified.
Inasmuch as potential causes
of breast cancer can be “ruled in,” the court finds that it is
possible, in a given instance, to perform a reliable differential
diagnosis to determine the cause of an individual’s breast
cancer, contrary to defendants’ contention that such methodology
is per se unreliable.
As plaintiff points out, other courts in
the HRT litigation have reached similar conclusions.
See, e.g.,
Scroggin v. Wyeth (In re Prempro Prods. Liab. Litig.), 586 F.3d
547 (8th Cir. 2009) (upholding use of differential diagnosis as a
reliable methodology for determine the cause of the plaintiff’s
breast cancer); Rivera Adams v. Wyeth, No. 03-1713, 2010 WL
5072061, at *4 (D.P.R. Dec. 3, 2010) (same; admitting Dr.
3
In support of the argument that the causes of breast
cancer are unknown, defendants rely not on scientific data, but
primarily on excerpts from Dr. Wertheimer’s deposition testimony.
Specifically, Dr. Wertheimer confirmed at his deposition that he
was quoted in a 1996 newspaper article as saying “no one really
knows or understands what causes breast cancer.” (Def.’s Mot. to
Exclude, Ex. 11, Wertheimer Dep. at 31-32). He went on to
testify, however, that this statement was accurate in 1996,
suggesting that his views have changed and the medical research
has revealed new findings since that time. (Id.). In any event,
to the extent that Dr. Wertheimer’s prior statements conflict
with his current testimony, this affects the weight rather than
the admissibility of his testimony.
11
Wertheimer’s use of differential diagnosis to determine the cause
of the plaintiff’s breast cancer).4
C.
Reliability of Dr. Wertheimer’s “Symptoms” Theory
Defendants next challenge the reliability of what they
call Dr. Wertheimer’s “symptoms” theory.
They summarize this
theory as follows: postmenopausal women who exhibit menopausal
symptoms (“symptomatic women”) have low levels of natural
estrogen, and postmenopausal women with low levels of natural
estrogen are at a lower risk of breast cancer absent HRT drug
use; therefore, symptomatic women are at a lower risk of breast
cancer absent HRT drug use.
In attacking this symptoms theory,
defendants note that Dr. Wertheimer has conducted no studies or
published any articles on this topic, and that his premises are
contradicted by the results of two independent medical studies
(the Farhat and Huang studies).
4
Defendants are correct that plaintiff has presented no
evidence that differential diagnosis is a generally accepted
methodology in the breast cancer community (though it bears
mentioning that defendants, while not the burden-carrying
parties, have presented no evidence showing that differential
diagnosis has been rejected in the breast cancer community).
However, general acceptance in the relevant scientific community
is only one of the Daubert factors, and, in light of the broad
acceptance of differential diagnosis in the medical community at
large, the absence of such evidence here does not sway the court
to exclude Dr. Wertheimer’s testimony.
12
Dr. Wertheimer’s theory does rely in part on the
premise that symptomatic women -- and, specifically, symptomatic
women whose menopausal symptoms improve after taking HRT drugs -have low levels of natural estrogen.
From this premise he is
able to conclude that plaintiff, a symptomatic woman whose
symptoms improved after taking HRT drugs, did not have sufficient
natural estrogen to cause her hormone dependent breast cancer,
and that exogenous hormones in the form of HRT drugs were thus
the likely cause of her disease.
Although it is true that Dr.
Wertheimer has not personally conducted any tests of his theory,
peer-reviewed medical publications cited by Dr. Wertheimer
conclude that the exhibition of certain menopausal symptoms
(e.g., vasomotor symptoms such as night sweats and hot flashes,
as well as vaginal atrophy) are a sign of estrogen deficiency.
(Wertheimer Rep. at 14 n.45 (citing Notelovitz, Clinical Opinion:
The Biological and Pharmacological Principles of Estrogen Therapy
for Symptomatic Menopause, 8(1) Medscape Gen. Med. 85 (2006);
Yasui, Serum Estrogen Level After Hormone Therapy and Body Mass
Index in Postmenopausal and Bilaterally Ovariectomized Women, 50
Maturitas 19-29 (2005))).
He also cites research showing that
menopausal symptoms are “an important biomarker of a woman’s
reduced risk of developing breast cancer.”
(Id. at 14 n.46
(citing Cuzik, Treatment Emergent Endocrine Symptoms and the Risk
13
of Breast Cancer Recurrence -- A Retrospective Analysis of the
ATAC trial, 9(12) Lancet Oncol. 1143-48 (2008); id. at 5, n.9
(citing, among others, Anderson, Prior Hormone Therapy and Breast
Cancer Risk in the Women’s Health Initiative Randomized Trial of
Estrogen Plus Progestin, 55(2) Maturitas 103-15 (2006))).
Once again, defendants do not address this medical
literature, nor do they challenge Dr. Wertheimer’s utilization of
the literature in forming his opinions.
They do, however, claim
that Dr. Wertheimer’s conclusions are rebutted by the results of
the Farhat and Huang studies, which, defendants argue, disprove
the theory that the presence of menopausal symptoms is indicative
of low natural estrogen levels and a corresponding lower risk of
breast cancer absent HRT drug use.
Setting aside whether these
studies do in fact conflict with Dr. Wertheimer’s findings,5
defendants’ arguments go to the conclusions reached rather than
the methodology employed by Dr. Wertheimer, and are therefore
insufficient to sustain a Daubert challenge.
Notably, the Eighth Circuit in Scroggin v. Wyeth upheld
a similar expert opinion against defendants’ Daubert challenge:
5
It appears that the Huang study actually confirms at
least one of Dr. Wertheimer’s premises. (See Pl.’s Opp., Ex. 3,
2011 Huang study, at 329 (“Conclusion: This is the first study to
report that women who ever experienced menopausal symptoms have a
substantially reduced risk of breast cancer.”)).
14
[P]ublished
research
had
concluded
that
hormone-receptor-positive tumors need hormones to grow,
that menopausal symptoms result from hormone deficiency,
and that there is a link between breast cancer and
hormone replacement therapy. See Lauzon v. Senco Prods.,
Inc., 270 F.3d 681, 693 (8th Cir. 2001) (noting that
“scientific reliability can also be shown by proof that
the research and analysis supporting the proffered
conclusions have been subjected to normal scientific
scrutiny through peer review and publication”).
Knowing that Scroggin’s breast cancer was hormone
dependent, Dr. Naftalis’s differential diagnosis sought
to determine the cause of Scroggin’s breast cancer by
ruling out the two possible sources of these hormones:
(1) Scroggin produced the hormones herself, or (2) they
came from the hormone replacement therapy she had taken
for the past eleven years. Scroggin presented evidence
that her menopausal symptoms were relieved by hormone
replacement therapy, confirming that her own body was
unable to produce sufficient hormones and therefore could
not be the cause.
The remaining source was the
combination
of
Premarin,
Provera,
and
Prempro.
Accordingly, Scroggin presented evidence establishing a
causal link between breast cancer and estrogen plus
progestin use, particularly for the length of time
Scroggin was taking the drugs.
586 F.3d at 566 (emphasis added & footnote omitted).
Attempting
to minimize the relevance of Scroggin here, defendants note that
the Eighth Circuit did not have the benefit of the subsequentlyreleased Farhat and Huang studies.
But, as noted, to the extent
that the Farhat and Huang studies conflict with the research
relied upon by Dr. Wertheimer and presented to the court in
Scroggin, this goes to the weight rather than the admissibility
of Dr. Wertheimer’s testimony.
The court concludes that Dr.
15
Wertheimer’s symptoms theory has a reliable foundation.6
D.
Soundness of Dr. Wertheimer’s Differential Diagnosis
Defendants claim that, even if differential diagnosis
can reliably be used to determine the cause of an individual’s
breast cancer, Dr. Wertheimer failed to conduct a proper
differential diagnosis of plaintiff.
The court considers each of
defendants’ challenges to Dr. Wertheimer’s differential
diagnosis.
6
In their reply, defendants argue that plaintiff (in her
opposition) and Dr. Wertheimer (in his deposition) have raised a
new “fluctuation theory” under which it is the E+P drugs’ “change
in hormone levels” that causes breast cancer, regardless of a
woman’s baseline risk. (Defs.’ Reply at 9-10). Stated
differently, E+P increases the relative risk of breast cancer in
all women regardless of whether they are symptomatic. (Pl.’s
Opp. at 9). Defendants are correct that this theory is neither
discussed in Dr. Wertheimer’s expert report nor is it
specifically applied to plaintiff’s case, though he does include
a single sentence opining that “E+P increases a woman’s risk of
developing breast cancer regardless of her baseline risk and
regardless of her baseline exposure,” without any supporting
analysis. (Wertheimer Rep. at 13). Rather than attempting to
piece together and evaluate this theory from various sources,
however, it suffices to say that the symptoms theory -- which
does appear in Dr. Wertheimer’s report -- has a reliable
foundation. Inasmuch as Dr. Wertheimer has not applied the
fluctuation theory to plaintiff’s case (i.e., to explain how
defendants’ HRT drugs thereby caused plaintiff’s breast cancer),
plaintiff may not pursue this theory at trial.
16
1.
Hormone-Dependency of Plaintiff’s Breast Cancer
Defendants first attack Dr. Wertheimer’s base
assumption that plaintiff’s ER/PR positive tumor required
hormones (either natural or pharmaceutical) to grow.
They
highlight an excerpt from Dr. Wertheimer’s report, wherein he
acknowledges that ER positive tumors can develop in “hormone
independent” ways:
As cancer progresses it can develop additional growth
pathways that can allow it to grow without the same
reliance on hormones as it initially had. Other growth
factors, which were initially “turned on” by estrogen and
progestin, can develop mutations allowing the cancer to
grow without a further complete dependence on estrogen.
. . . Nevertheless, it is generally accepted that breast
cancers expressing ER and/or PR receptors developed into
cancer and grew, at least initially, in a hormone
dependent fashion. [Footnote omitted] Once developed,
these hormone dependent tumors can mutate and develop
hormone independent biological pathways to progress and
even metastasize.
(Wertheimer Rep. at 13).
In the footnote omitted above, Dr. Wertheimer cites
publications supporting the “generally accepted” view that breast
cancers with ER and/or PR positive receptors at least initially
grew into cancer in a hormone dependent fashion.
This, in turn,
provides a sufficient foundation for Dr. Wertheimer’s opinion
that this plaintiff’s ER/PR positive breast cancer, more likely
than not, grew in a hormone dependent fashion.
The follow-up
sentence where he recognizes that hormone dependent tumors can
17
later develop “hormone independent” pathways does not diminish
his fundamental opinion.
If plaintiff’s tumor developed into
malignant cancer in a hormone dependent fashion, as Dr.
Wertheimer opines and as supported by the fact that plaintiff’s
tumor was ER/PR positive, then Dr. Wertheimer’s mere
acknowledgment that hormone dependent tumors can sometimes
develop hormone independent pathways is not inconsistent with his
stated view.
2.
Timing of Plaintiff’s Breast Cancer
Defendants next point to portions of Dr. Wertheimer’s
testimony indicating that he could not identify precisely when
plaintiff’s invasive breast cancer developed.
Since Dr.
Wertheimer does not know when plaintiff’s cancer became invasive,
defendants contend, he cannot reliably say whether her cancer was
“fueled” by defendants’ HRT drugs.
mark.
This argument misses the
Again, Dr. Wertheimer started with the premise that
plaintiff’s ER/PR positive breast cancer required hormones to
grow.
After eliminating natural hormones as a potential cause
(based on plaintiff’s menopausal symptoms and the HRT drugs’
relief of those symptoms), he isolated exogenous hormones from
defendants’ HRT drugs as the remaining cause.
While Dr.
Wertheimer cannot state with absolute certainty that plaintiff’s
breast cancer became invasive only after she ingested HRT drugs,
18
absolute certainty is not required -- he need only state his
causation opinions in terms of “reasonable probability.”
Rohrbough v. Wyeth Labs., Inc., 916 F.2d 970, 972 (4th Cir. 1990)
(citing Hovermale v. Berkeley Springs Moose Lodge No. 1483, 271
S.E.2d 335, 340 (W. Va. 1980)).
Here, Dr. Wertheimer concluded
to a reasonable degree of medical probability (and by way of
reliable means) that HRT drugs caused plaintiff’s hormone
dependent cancer.
(Wertheimer Rep. at 17).
It was not necessary
for Dr. Wertheimer to pinpoint precisely when plaintiff’s breast
cancer became invasive.
Defendants can challenge Dr.
Wertheimer’s conclusions through vigorous cross examination.
3.
Exclusion of Natural Estrogen as a Potential Cause
Defendants next claim that Dr. Wertheimer did not
adequately exclude natural estrogen as a potential cause of
plaintiff’s breast cancer.
Because Dr. Wertheimer does not know
how much natural estrogen plaintiff was producing, defendants
argue, he cannot establish that her cancer was not caused by
natural estrogen instead of HRT drugs.
In evaluating whether Dr. Wertheimer properly
considered alternative causes in performing his differential
diagnosis, the court is guided by the Fourth Circuit’s decision
in Cooper:
19
A medical expert’s opinion based upon differential
diagnosis normally should not be excluded because the
expert has failed to rule out every possible alternative
cause of a plaintiff's illness. See Westberry, 178 F.3d
at 265 (citations omitted).
In such cases, the
alternative causes suggested by a defendant normally
affect the weight that the jury should give the expert's
testimony and not the admissibility of that testimony.
See id. at 265 (citations omitted). However, . . . if an
expert utterly fails to consider alternative causes or
fails to offer an explanation for why the proffered
alternative cause was not the sole cause, a district
court is justified in excluding the expert’s testimony.
259 F.3d at 202 (some citations omitted).
In his expert report,
Dr. Wertheimer considered and excluded natural estrogen as a
potential cause:
In postmenopausal women, there are only two possible
sources of the female hormones necessary to develop and
grow hormone dependent cancer: endogenous hormones
(estrogen and progesterone that are naturally produced in
a woman’s body) or exogenous hormones (such as E+P).
* * * *
I consider what evidence there is of a woman’s levels of
endogenous estrogen as one factor in forming my causation
opinion. Certain symptoms and radiographic findings can
be important. For example, vasomotor symptoms [e.g.,
hot flashes and night sweats] are often a sign of low
endogenous estrogen levels. If these symptoms improve or
go away upon treatment with exogenous hormones then that
is confirmation that low estrogen levels played an
important role in causing the symptoms.
Similarly,
vaginal or urogenital atrophy symptoms are a strong
indication that the woman has very low tissue levels of
estrogen.
* * * *
Mrs. Hines reported that, prior to taking hormone
therapy, she experienced menopausal symptoms including
severe hot flashes, night sweats, and vaginal dryness.
These symptoms improved on hormone therapy and returned
20
to some degree after cessation of hormone therapy.[]
This clinical information strongly supports that Mrs.
Hines was a “low hormone producing” woman at and around
the time of menopause.
(Wertheimer Dep. at 13, 14, 15).
Although it is true that Dr.
Wertheimer does not know exactly how much natural estrogen
plaintiff was producing and thus cannot exclude natural estrogen
as a potential cause with absolute certainty, this does not
preclude the admission of his testimony.
It suffices to say that
he considered natural estrogen as an alternative cause and
offered a plausible explanation as to why it was not the sole
cause.
See Cooper, 259 F.3d at 202.
4.
Exclusion of Other Potential Causes
Defendants further contend that Dr. Wertheimer failed
to rule out plaintiff’s baseline risk factors, such as breast
density, family history of breast cancer, and her age.
The
Eighth Circuit in Scroggin best summed up the flaws with this
argument:
We find unpersuasive the contention that Dr. Naftalis's
testimony should not have been admitted because Scroggin
has some breast cancer risk factors and a family history
of breast cancer. Dr. Naftalis sufficiently established
that hormones were necessary to the development of
Scroggin's tumors and conducted her differential
diagnosis from this starting point. Although not
necessary to the formation of her opinion, Dr. Naftalis
addressed the known causes of breast cancer and possible
risk factors. Wyeth and Upjohn argue that this review
was insufficient, but Dr. Naftalis’s “explanations as to
conclusions not ruled out went to weight and not
21
admissibility.”
* * * *
Dr. Naftalis was able to testify that Scroggin's breast
cancer would not have developed without hormone
replacement therapy because Scroggin's body was not
producing sufficient amounts of hormones to allow
hormone-receptor-positive tumors to develop. Thus, Dr.
Naftalis ruled out the other possible cause of Scroggin's
breast cancer, and her expert testimony was properly
admitted.
586 F.3d at 566 (emphasis added & citations omitted).
Applying the reasoning from Scroggin here, the court
likewise finds that Dr. Wertheimer sufficiently established the
necessity of hormones in the development of plaintiff’s breast
cancer (as discussed supra), and that he gave adequate
consideration to alternative causes and risk factors.
Regarding
family history, Dr. Wertheimer observed that the plaintiff’s
“family history is remarkable for breast cancer in her daughter,
who was diagnosed . . . with invasive ductal breast cancer with
negative hormone receptors.”
(Wertheimer Rep. at 16).
As he
explained, however, the medical literature indicates that “family
history is a more significant risk for ER [negative] breast
cancers,” and plaintiff was diagnosed with ER/PR positive breast
cancer, a type of cancer generally requiring hormones to grow.
(Id. at 16 n.61 (citing, among others, Cummings, Sex Hormones,
Risk Factors, and Risk of Estrogen Receptor-Positive Breast
Cancer in Older Women: A Long Term Prospective Study, Cancer
22
Epidemiol Biomarkers at 1047, 1049, 1050 (2005))).
Dr.
Wertheimer concluded that the hormones necessary to the
development of the plaintiff’s breast cancer were not
attributable to “family history.”
(Id.).
Regarding breast density, Dr. Wertheimer noted that
plaintiff did have dense breasts.
(Id.).
He pointed out,
though, that while breast density typically decreases during
menopause through a process called “involution,” the density of
plaintiff’s breasts remained the same while she was on E+P.
(Id.).
Noting that HRT drugs are known to slow or reserve the
“normal involution” process, he found that, “[t]o the extent that
her breast density increased Mrs. Hines’s risk of breast cancer
and made detection more difficult, that risk factor was
aggravated and contributed to by E+P use.”
(Id. at 16-17).
Dr.
Wertheimer further observed that Hines was at a lower risk of
developing ER/PR positive breast cancer because she did not
consume alcohol, had no significant exposure to ionizing
radiation, was not obese, and (as previously discussed) had
experienced menopausal symptoms that were alleviated by HRT
drugs.
Defendants disagree with Dr. Wertheimer’s explanations as
to alternative causes, but these challenges go to the weight, not
the admissibility, of his testimony.
23
In sum, the court finds that Dr. Wertheimer’s testimony
passes the Daubert reliability threshold.
Defendants, to be
sure, mount a variety of challenges to Dr. Wertheimer’s opinions.
But since the court has already found that it is possible to
perform a reliable differential diagnosis to determine the cause
of an individual’s breast cancer, the ultimate question under
Rule 702 is whether Dr. Wertheimer conducted a reliable
differential diagnosis of plaintiff.
Trial courts making the
reliability determination have “broad latitude to consider
whatever factors bearing on validity that the court finds to be
useful.”
Westberry, 178 F.3d at 261.
And so, rather than
turning to the illustrative list of factors set forth in Daubert,
the court finds guidance in factors formulated specifically to
evaluate whether a differential diagnosis meets the Daubert
reliability standard:
(1) Did the expert make an accurate diagnosis of the
nature of the disease? (2) Did the expert reliably rule
in the possible causes of it? (3) Did the expert reliably
rule out the rejected causes? If the court answers “no”
to any of these questions, the court must exclude the
ultimate conclusion reached.
Tamraz v. Lincoln Elec. Co., 620 F.3d 665, 674 (6th Cir. 2010);
accord In re Paoli Railroad Yard PCB Litigation, 35 F.3d 717,
760-62 (3d Cir. 1994).
24
Here, (1) plaintiff’s breast cancer diagnosis is not
disputed; (2) Dr. Wertheimer reliably ruled in both natural and
pharmaceutical hormones as possible causes of plaintiff’s breast
cancer based upon the ER/PR positive status of plaintiff’s breast
cancer (as supported by peer-reviewed medical literature finding
that ER/PR positive cancer is generally dependent upon hormones
to grow); and (3) he reliably ruled out natural hormones as a
potential cause of plaintiff’s breast cancer based on her
exhibition of menopausal symptoms and the effectiveness of HRT
drugs in treating those symptoms (as supported by peer-reviewed
medical literature finding that symptomatic women have low levels
of natural estrogen).
Thus, Dr. Wertheimer conducted a reliable
differential diagnosis.
E.
Relevancy of Dr. Wertheimer’s Opinions
Defendants lastly contend that Dr. Wertheimer’s
opinions do not satisfy the “but for” causation standard and are
therefore irrelevant, emphasizing, among other things,7 that Dr.
Wertheimer testified he does not know what “initiates” the first
cancer cell.
This contention reveals an underlying dispute
between the parties concerning how E+P causes breast cancer.
7
This part of defendants’ brief (Part IV) rehashes a
number of arguments that the court has already addressed.
25
Plaintiff and Dr. Wertheimer maintain that E+P causes breast
cancer through “promotion” rather than “initiation,” meaning that
the drugs transform benign abnormalities into malignant tumors.
Put another way, plaintiff does not claim that E+P “initiated”
the first abnormal cell that ultimately led to her hormone
dependent cancer, but only that it “promoted” its growth by
providing necessary hormonal fuel.
Defendants, on the other
hand, seem to assert that if HRT did not cause the initial
abnormality, then it did not cause plaintiff’s breast cancer.
Regardless of defendants’ disagreement with the promotion theory,
though, it does appear to satisfy the causation standard, for the
gist of the theory is that plaintiff’s cancer would not have
become invasive but for her use of HRT drugs.
Inasmuch as the court concludes that Dr. Wertheimer’s
causation testimony rests on a reliable foundation and is
relevant, his expert opinion is admissible under Rule 702.
IV.
Plaintiff’s Motion to Exclude
According to plaintiff, defendants have designated
three causation experts (Drs. Chodosh, Meile, and Levy) who will
testify that E+P does not generally cause breast cancer in women.
Plaintiff contends that this testimony “flies in the face of the
26
overwhelming consensus of scientific opinion, epidemiological
study results, ecological data and opinions on biologic
plausibility.”
(Pl.’s Mot. to Exclude at 2).
Based upon the
inconsistency between the opinions of defendants’ experts and the
rest of the scientific community, plaintiff maintains that
defendants cannot meet their burden of demonstrating that the
testimony is relevant and reliable.
The Court in Daubert made clear that a district court’s
reliability analysis must focus on the “principles and
methodology” employed by the expert, not on the conclusions
reached.
509 U.S. at 594-95.
In this sense, plaintiffs’ motion
to exclude the testimony of defendants’ general causation experts
is not “a true Daubert challenge,” as she calls into question
neither the principles nor the methodology underlying the
experts’ opinions.
(4th Cir. 2003).
See TFWS, Inc. v. Schaefer, 325 F.3d 234, 240
Indeed, plaintiff does not discuss any of the
four Daubert factors that are to guide the court’s gate-keeper
inquiry.
She instead argues that the experts’ conclusions “are
grossly out of step with a consensus in the relevant medical
community” and must therefore be excluded.
Inasmuch as this
challenge goes to the weight of the experts’ testimony, and not
its admissibility, plaintiff’s motion is without merit.
27
V.
Conclusion
For the foregoing reasons, the court ORDERS as follows:
1.
That defendants’ motion to exclude Dr. Wertheimer’s
testimony be, and it hereby is, denied.
2.
That plaintiff’s motion to exclude expert testimony
that combination hormone therapy does not generally
cause breast cancer be, and it hereby is, denied.
The Clerk is directed to forward copies of this written
opinion and order to all counsel of record.
DATED: July 8, 2011
John T. Copenhaver, Jr.
United States District Judge
28
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