**MENTOR'S SILICONE GEL-FILLED BREAST IMPLANTS (P030053)**

**SUMMARY OF CERTAIN CLINICAL ISSUES PRESENTED TO FDA'S GENERAL AND
PLASTIC SURGERY DEVICES ADVISORY PANEL**

Based on communications with the Food and Drug Administration ("FDA"),
Mentor is submitting this summary overview of certain key clinical
issues concerning its silicone gel-filled breast implants, to facilitate
the Panel's evaluation of these products. This summary supplements, and
is not intended to replace, the more detailed package of PMA information
previously provided by Mentor in CD format.

I.  **CLINICAL RELEVANCE OF SILICONE BREAST IMPLANT GENERATIONS**

The literature recognizes three distinct generations of implants:[^1]^/^

![](media/image1.wmf)The relevance and value of the silicone gel-filled
breast implant literature, as it relates to generations, are as follows:

A.  **Potential Health Consequences**

Information concerning the biological effects of silicone may be validly
gleaned from the extensive universe of medical literature on all
generations of implants. Health consequences literature on earlier
generations of silicone gel-filled implants in fact provides us with a
measure of the worst case over a longer period of time of use, given the
higher rates of exposure ([e.g.]{.underline}, from rupture) associated
with those implants.

B.  **Mechanical Characteristics**

In contrast to potential health consequences, literature relating to the
mechanical characteristics ([e.g.]{.underline}, rupture and migration)
should be evaluated on a generation-by‑generation basis. Mentor's
implants are third generation ([i.e.]{.underline}, they have a low-bleed
elastomeric shell with a barrier layer and thick gel). All literature
pertaining to third generation implants is directly applicable to the
performance of Mentor's PMA products, given the similarity in design and
chemical composition of all third generation implants.

Reliance on prior generation literature would not be appropriate to
evaluate rupture and related mechanical performance characteristics,
given the substantially different design profiles of the prior
generations. Marked differences in rupture rate and related mechanical
performance between generations have been clearly demonstrated in a
number of studies.[^2]^/^

II. **EXTENT OF MENTOR'S FOLLOW-UP IN ITS CORE STUDY**

Mentor obtained 3-year follow-up on a majority of the patients (n=665)
prior to Mentor's August 2004 submission. Among those patients eligible
for follow-up at time of database closure, 94% had returned for the
3-year follow-up visit. Follow-up rates also were consistently high for
all enrolled patients in the study at the 1- and 2-year visits (94%
overall). As of 2005 ([i.e.]{.underline}, post-submission), 3-year
follow-up has been obtained for 812 enrolled patients. Data from this
latest follow-up shows no statistical difference in Kaplan-Meier
complications from the August 2004 submission.

III. **THE WEIGHT OF EVIDENCE SUPPORTING NO ASSOCIATION BETWEEN
     CONNECTIVE TISSUE DISEASE (CTD) AND RELATED SYMPTOMS, AND SILICONE
     BREAST IMPLANTS**

It is well-established that the issue of CTD is best addressed by
well-designed, controlled epidemiological studies. These studies
examined the potential association between both ruptured and intact
silicone breast implants and CTD and/or related symptoms.

As noted below,[^3]^/^ the weight of the evidence from the literature
evaluating silicone implants generally ([i.e.]{.underline}, irrespective
of rupture), shows no association between these products and CTD and
related symptoms. The sum total of patients with breast implants in
these studies exceeds 34,000 (patients from the same cohort reported in
multiple studies were counted only once).

+-----------------------+-----------------------+-----------------------+
| Berner et al. 2002    | Fryzek et al. 2001    | Kjøller et al. 2004   |
|                       |                       |                       |
| Brinton et al. 2004   | Gabriel et al. 1994   | Laing et al. 2001     |
|                       |                       |                       |
| Breiting et al. 2004  | Gaubitz et al. 2002   | Lipworth et al. 2004  |
|                       |                       | (meta-analysis)       |
| Burns et al. 1996     | Giltay et al. 1994    |                       |
|                       |                       | Nyrén et al. 1998     |
| Edworthy et al. 1998  | Goldman et al. 1995   |                       |
|                       |                       | Park et al. 1998      |
| Englert et al. 1996   | Hennekens et al. 1996 |                       |
|                       |                       | Sánchez-Guerrero et   |
| Englert et al. 2001   | Hochberg et al. 1996  | al. 1995              |
|                       |                       |                       |
| Friis et al. 1997     | Hölmich et al. 2003   | Schusterman et al.    |
|                       |                       | 1993                  |
|                       | Janowsky et al. 2000  |                       |
|                       | (meta-analysis)       | Strom et al. 1994     |
|                       |                       |                       |
|                       | Jensen et al. 2001    | Weisman et al. 1988   |
|                       |                       |                       |
|                       | Kjøller et al. 2001   | Wells et al. 1994     |
|                       |                       |                       |
|                       |                       | Williams et al. 1997  |
+-----------------------+-----------------------+-----------------------+

Likewise, the weight of the evidence from the following studies support
no association between [ruptured]{.underline} implants and CTD and
related symptoms:

  ----------------------- ----------------------- -----------------------
  **Citation**            **N**                   **Average Follow-up
                                                  (Years)**

  Hölmich et al.          238                     14
  2003[^4]^/^                                     

  Berner et al.           32                      7
  2002[^5]^/^                                     

  Gaubitz et al.          90                      9.1
  2002[^6]^/^                                     

  Brown et al.            344                     16.5
  2001[^7]^/^                                     

  Fryzek et al.           1,280                   13
  2001[^8]^/^                                     

  Wolfe and Anderson      508                     Not Applicable (Case
  1999[^9]^/^                                     Control Study)
  ----------------------- ----------------------- -----------------------

Importantly, these epidemiologic studies reflect worst-case exposure \--
that is, they included patients with prior generation implants
associated with higher rupture rates and exposure than has been
demonstrated for the current third generation implants.

Although patients in the Core study were monitored for CTD and related
symptoms, as noted above, it is well-established that the issue of CTD
is best addressed by well-designed, controlled epidemiological studies.
Nevertheless, the occurrence of CTD in the Core Study was well below the
published rates for the individual diseases in the general population.

  -----------------------------------------------------------------------
  **CTD Diagnosis**            **Core Gel      **Published Rates in
                               Study           General Population**
                               Incidence**     
  ---------------------------- --------------- --------------------------
  Hashimoto thyroiditis/       2 patients      0.8% (including Hashimoto
  autoimmune hypothyroidism    (0.2%)          and other) (Jacobson et
                                               al. 1997)[^10]^/^

  Fibromyalgia                 2 patients      3.4% (Wolfe et al.
                               (0.2%)          1995)[^11]^/^

  Pyoderma gangrensosum        1 patient       0.6% (Mancini et al.
                               (0.1%)          2002)[^12]^/^

  Rheumatoid arthritis         1 patient       0.9% (Jacobson et al.
                               (0.1%)          1997)[^13]^/^
  -----------------------------------------------------------------------

Two very common symptoms experienced by the general population are
fatigue and joint pain. The appropriate method to investigate whether
there is a causal relationship between these symptoms and silicone
breast implants is well-designed, controlled epidemiological studies. As
summarized below, it is well established through such studies that joint
pain and fatigue are no more common in women with breast implants than
in the general population. Also as summarized below, it is well
established that joint pain and fatigue are no different in women with
ruptured versus intact implants and women with intracapsular versus
extracapsular ruptures.

+---------------+------+---------------------+------------------------+
| **Joint Pain  |      |                     |                        |
| and Women     |      |                     |                        |
| with Breast   |      |                     |                        |
| Implants:**   |      |                     |                        |
|               |      |                     |                        |
| *             |      |                     |                        |
| *Epidemiology |      |                     |                        |
| Studies**     |      |                     |                        |
+===============+======+=====================+========================+
|               |      | **Findings**        |                        |
+---------------+------+---------------------+------------------------+
| **Citation**  | **   | **Relative Risks**  | **Odds Ratios (95%     |
|               | Desi |                     | CI)**                  |
|               | gn** |                     |                        |
+---------------+------+---------------------+------------------------+
| Kjøller et    | Co   | 1.1                 | 0.7--1.8               |
| al.           | hort |                     |                        |
| (             |      |                     |                        |
| 2004)[^14]^/^ |      |                     |                        |
+---------------+------+---------------------+------------------------+
| Hölmich et    | Co   | 1.0                 | 0.5--1.8: patients w/  |
| al.           | hort |                     | ruptured vs. intact    |
| (             |      | 1.4                 | implants\              |
| 2003)[^15]^/^ |      |                     | 0.4--4.7: patients w/  |
|               |      |                     | extracapsular rupture\ |
|               |      |                     | vs. intact implants    |
+---------------+------+---------------------+------------------------+
| Brown et al.  | Co   | 1.4                 | 0.8-2.4: patients w/   |
| (             | hort |                     | extracapsular\         |
| 2002)[^16]^/^ |      |                     | vs. intracapsular      |
|               |      |                     | rupture                |
+---------------+------+---------------------+------------------------+
| Berner et al. | Mat  | No significant      | ---                    |
| (             | ched | difference          |                        |
| 2002)[^17]^/^ | Pair |                     |                        |
|               | Anal | 62.5% in cancer     |                        |
|               | ysis | patients with       |                        |
|               |      | implants            |                        |
|               |      |                     |                        |
|               |      | 60.9% in cancer     |                        |
|               |      | patients without    |                        |
|               |      | implants            |                        |
+---------------+------+---------------------+------------------------+
| Gaubitz et    | Co   | No significant      | ---                    |
| al.           | hort | difference          |                        |
| (             |      |                     |                        |
| 2002)[^18]^/^ |      | 79.2% in patients   |                        |
|               |      | with ruptured       |                        |
|               |      | implants (by MRI)   |                        |
|               |      |                     |                        |
|               |      | 74.2% in patients   |                        |
|               |      | with intact         |                        |
|               |      | implants            |                        |
+---------------+------+---------------------+------------------------+
| Fryzek        | Co   | 1.1 (not            | ---                    |
| (             | hort | significant)        |                        |
| 2001)[^19]^/^ |      | patients with       |                        |
|               |      | implant leakage\    |                        |
|               |      | vs. patients with   |                        |
|               |      | no local            |                        |
|               |      | complications       |                        |
+---------------+------+---------------------+------------------------+
| Park et al.   | Co   | 1.07                | 0.49-2.32:             |
| (             | hort |                     | augmentation patients\ |
| 1998)[^20]^/^ |      | 1.01                | 0.56-1.84:             |
|               |      |                     | reconstruction         |
|               |      |                     | patients               |
+---------------+------+---------------------+------------------------+
| Giltay et al. | Co   | 2.28                | 1.37-3.81              |
| (             | hort |                     |                        |
| 1994)[^21]^/^ |      |                     |                        |
+---------------+------+---------------------+------------------------+
| Wells et al.  | Co   | 1.929               | 0.521-7.142            |
| (             | hort |                     |                        |
| 1994)[^22]^/^ |      |                     |                        |
+---------------+------+---------------------+------------------------+

+---------------+------+-----------------------+-----------------------+
| **Fatigue and |      |                       |                       |
| Women with    |      |                       |                       |
| Breast        |      |                       |                       |
| Implants:**   |      |                       |                       |
|               |      |                       |                       |
| *             |      |                       |                       |
| *Epidemiology |      |                       |                       |
| Studies**     |      |                       |                       |
+===============+======+=======================+=======================+
|               |      | **Findings**          |                       |
+---------------+------+-----------------------+-----------------------+
| **Citation**  | **   | **Relative Risks**    | **Odds Ratios (95%    |
|               | Desi |                       | CI)**                 |
|               | gn** |                       |                       |
+---------------+------+-----------------------+-----------------------+
| Kjøller et    | Co   | 1.6                   | 0.9--2.8              |
| al.           | hort |                       |                       |
| (             |      |                       |                       |
| 2004)[^23]^/^ |      |                       |                       |
+---------------+------+-----------------------+-----------------------+
| Hölmich et    | Co   | 0.7                   | 0.3--1.6: patients w/ |
| al.           | hort |                       | extracapsular rupture |
| (             |      | 1.9                   | vs. intact implants   |
| 2003)[^24]^/^ |      |                       |                       |
|               |      |                       | 0.7--5.2: patients w/ |
|               |      |                       | extracapsular rupture |
|               |      |                       | vs. intact implants   |
+---------------+------+-----------------------+-----------------------+
| Brown et al.  |      | 1.1                   | 0.5-2.1: patients w/  |
| (             |      |                       | extracapsular\        |
| 2002)[^25]^/^ |      |                       | vs. intracapsular     |
|               |      |                       | rupture               |
+---------------+------+-----------------------+-----------------------+
| Berner et al. | Mat  | No significant        |                       |
| (             | ched | difference            |                       |
| 2002)[^26]^/^ | Pair |                       |                       |
|               | Anal | 40.6% in cancer       |                       |
|               | ysis | patients with         |                       |
|               |      | implants              |                       |
|               |      |                       |                       |
|               |      | 34.4% in cancer       |                       |
|               |      | patients without      |                       |
|               |      | implants              |                       |
+---------------+------+-----------------------+-----------------------+
| Gaubitz et    | Co   | No significant        |                       |
| al.           | hort | difference            |                       |
| (             |      |                       |                       |
| 2002)[^27]^/^ |      | 45.8% in patients     |                       |
|               |      | with ruptured         |                       |
|               |      | implants (by MRI)     |                       |
|               |      |                       |                       |
|               |      | 47.0% in patients     |                       |
|               |      | with intact implants  |                       |
+---------------+------+-----------------------+-----------------------+
| Fryzek        | Co   | 1.0 (not significant) | Patients with implant |
| (             | hort |                       | leakage\              |
| 2001)[^28]^/^ |      |                       | vs. patients with no  |
|               |      |                       | local complications   |
+---------------+------+-----------------------+-----------------------+
| Park et al.   | Co   | 2.01                  | 0.74-5.56:            |
| (             | hort |                       | augmentation patients |
| 1998)[^29]^/^ |      | 0.76                  |                       |
|               |      |                       | 0.37-1.60:            |
|               |      |                       | reconstruction        |
|               |      |                       | patients              |
+---------------+------+-----------------------+-----------------------+
| Wells et al.  | Co   | 1.379                 | 1.379 (95% CI         |
| (             | hort |                       | 0.547-3.310)          |
| 1994)[^30]^/^ |      |                       |                       |
+---------------+------+-----------------------+-----------------------+

IV. **RUPTURE RATE AND HEALTH CONSEQUENCES**

Any evaluation of rupture ([e.g.]{.underline}, rates, intracapsular
versus extracapsular, asymptomatic versus symptomatic, issues of
progression, and change over time) must be reviewed first and foremost
in light of what is known regarding the potential health consequences
resulting from ruptures. As noted above, findings from a number of
well-designed, controlled epidemiology studies, taken together, do not
support an association between ruptured silicone breast implants and
systemic disease or symptoms. These epidemiological findings of no
systemic health consequences should guide and override any perceived
limitations with respect to individual evaluations of rupture rate and
progression.

The Core data provide meaningful information concerning the expected
rupture rate through three years. These findings are consistent with
literature evaluating overt ([i.e.]{.underline}, patient and/or
physician-recognized) ruptures in third generation devices for a similar
or longer period of time (Henrickson et al. 2003 and third generation
subset analysis of Kjøller).[^31]^/^ In Henrickson et al. (2003), 971
women (85% augmentation, 15% reconstruction) were followed up to two
years post surgery with no overt ruptures reported. In an unpublished
third generation subanalysis of Kjøller et al. (2002) involving
augmentation patients (mean implantation time of 5 years; range of up to
9 years), only 2 of 509 implants ruptured (0.4%).

The Core findings are supported and extended by Mentor's PMA longer-term
data which evaluated overt and silent ([i.e.]{.underline}, asymptomatic)
ruptures of Mentor's third generation PMA implants out to 12 years
(Sharpe and Collis). The long-term rupture study conducted by Drs.
Sharpe and Collis evaluated by MRI the integrity of subglandular
textured Mentor implants up to 12 years in 101 augmentation patients.
Patients with Baker III/IV capsular contracture (considered by some to
be at higher risk for rupture[^32]) were included, as were patients with
prior surgical procedures ([e.g.]{.underline}, mastopexy). The
inframammary incision that was used in the Sharpe and Collis study also
was used in the majority of Augmentation patients in Mentor's Core
Study. The study's use of subglandular placement, which is associated
with a higher rate of capsular contracture ([see]{.underline} Kulmala et
al. 2004),[^33]^/^ provides a worst case evaluation of rupture risk.
Mentor's textured implants are representative of all implants used in
the Core Study, given the lack of an association between surface type
and complications reported both in the Core Study (Cox analysis) and in
the literature (Kulmala et al. 2004; mean follow-up 10.9 years).[^34]^/^

The objective of the statistical methodology used for the Sharpe and
Collis study was to provide a valid approach to estimate the cumulative
incidence of rupture based on these data. Mentor recognizes that
estimation of cumulative incidence over time is almost always estimated
based on longitudinal data, often using survival analysis methodology.
The Sharpe and Collis data, however, are cross-sectional. Specifically,
the data consisted of two elements for each implant: the age of the
implant (in years) and whether or not the MRI for the implant is called
a silent rupture. Standard methods to use such cross-sectional data to
estimate a cumulative incidence (or, equivalently, a survival curve)
were not available and, thus, an alternative statistical method was
employed.

The approach used, while not standard, was derived using standard
mathematical estimation methods, and is fully valid. Thus, it is
possible to estimate the cumulative incidence of rupture based on a
cross-sectional sample of implants. The approach employed standard
mathematical statistical methods, specifically maximum likelihood
estimation, to derive an appropriate estimate of the survival curve. A
jackknife method was then used to estimate the variance from which 95%
confidence intervals were obtained using the normal approximation.

This study provides several important findings concerning long-term
silent and overt rupture rates. There were no overt ruptures identified
among this population, and silent ruptures were not observed until
approximately 7 years after implantation. The rupture rate slowly
increased thereafter until, at 12 years, it was 15% (by patient) and 9%
(by implant). There were no confirmed extracapsular ruptures, and the
average age of implant at time of confirmed rupture was 9.61.6 years.

Like the Core findings, the Sharpe and Collis findings are consistent
with literature \-- specifically, a multi-site Danish study that
evaluated silent and overt third generation device ruptures for a
similar period of time (Hölmich et al. 2003).[^35]^/^ (The findings of
the Hölmich et al. 2003 study fall within the Sharpe and Collis study
confidence intervals.) Approximately 62% of the implants evaluated in
the Hölmich et al. 2003 study were third generation implants, which are
representative of Mentor's PMA products. Because third generation
implants have essentially equivalent materials and design, literature
assessing third generation implant rupture is directly relevant to
assessing product performance characteristics of Mentor's devices. As
with the Sharpe and Collis findings of no rupture through 7 years, the
authors of this study note that "third generation implants currently in
use are relatively durable for the first six to eight years *in situ*,
after which the rupture rate increases."[^36]^/^

In the Hölmich et al. (2003) study, two MRIs were performed on each
study implant, approximately 2 years apart. Third generation implants
ranged in age from approximately 3 to 12 years. Based on the MRI
results, 2-year cumulative incidence of implant rupture was estimated by
implant age category ([e.g.]{.underline}, 3-5, 6-7, 8-9, and 10-11
years). These estimates by age category were then combined (assuming a
piecewise exponential distribution within age category) to estimate a
cumulative rupture-free implant survival. Subtracting from one, this
provides an estimate of the cumulative incidence of implant rupture by
implant age.

Based on these cumulative estimates, and consistent with the Sharpe and
Collis study, the authors conclude "for modern \[third generation\]
implants intact 3 years after implantation, we estimated rupture-free
survival of 98% at 5 years and 83% to 85% at 10 years"[^37]^/^
([i.e.]{.underline}, 15% rupture, by implant). Other rates not specific
to third generation implants or not cumulative in nature are not
appropriate for estimating cumulative rupture incidence rates. For
example, the 3.6% rupture rate per year cited in this study for third
generation implants is not itself a cumulative rupture incidence rate,
and should not be used to calculate cumulative rupture incidence rate
because it does not take implant age into account. Likewise, the rate of
8.9% ruptures per year cited in the publication for all generations, is
not representative of third generation rates.

The Hölmich study evaluated patients who entered the study with implants
intact three years after implantation. This should not, however, impact
overall rupture rates based on the findings from other third generation
studies because, as noted above, other studies establish that third
generation implants do in fact remain intact through 3 years.[^38]^/^

-   Only one confirmed patient with ruptures among 1,007 patients in
    Mentor's Core Study after three years of follow-up;

-   No ruptures among 971 women in the first two years of follow-up in
    Henrickson et al. (2003): and

-   Two ruptures among the subset of 509 (0.4%) patients with third
    generation implants and a mean follow-up of 5 years in Kjøller et
    al. (2002) (based on a subanalysis of the original study).

In addition to information on silent rupture over time, the Danish data
([e.g.]{.underline}, Hölmich et al.) are important and informative in
helping to define progression of ruptures and extracapsular rupture
rates as well.

-   Progression: Hölmich et al. (2004)[^39]^/^ directly addressed
    progression of ruptures using MRI evaluations. Because a third
    generation subanalysis was not available for this aspect of the
    study, the findings on progression likely represent worst case. In
    this study, 90% of intracapsular ruptures showed no change at second
    MRI ([i.e.]{.underline}, two years later), and 84% of extracapsular
    ruptures remained stationary at second MRI.

-   Extracapsular ruptures: The extracapsular rupture rate for third
    generation devices was assessed in an unpublished subanalysis by the
    authors of the Hölmich publications, and found to be extremely low
    (0.8%).

V.  **EFFECTIVENESS DATA AND SUPPORTING LITERATURE**

    A.  **Core Study Findings**

Primary effectiveness measures were met for each cohort in the Core
Study, [i.e.]{.underline}, increase in cup size for Augmentation and
Revision patients; restoration of the breast mound for the
Reconstruction patients; and an increase in chest circumference in all
cohorts.

The following secondary effectiveness/quality of life measures also were
evaluated consistent with FDA guidance.

  ----------------------------- ------------------ -------------------- --------------
  **Instrument**                **Augmentation**   **Reconstruction**   **Revision**

  Body Esteem                                                           

  Rosenberg Body Esteem                                                 

  SF-36                                                                 

  Tennessee Self-Concept Scale                                          

  FLIC (Cancer)                                                         
  ----------------------------- ------------------ -------------------- --------------

A number of these scales focused on issues that are unrelated to breast
image and satisfaction with surgical outcome. For example, the Tennessee
Self-Concept Scale requires that the patient indicate the extent to
which she agrees with the following statements: "I am a moral failure;"
"Once in a while, I laugh at a dirty joke;" "I often act like I am 'all
thumbs;'" "I would rather win than lose in a game;" "At times I feel
like swearing;" "I should love my family more;" and "I do not like
everyone I know." Consequently, it is important to review the specific
subscales of each assessment tool to understand their relevance to
satisfaction in this population.

In the Augmentation cohort, an increase in self esteem was noted on the
Rosenberg Self Esteem Scale. There was no change on the overall score of
the Body Esteem Scale. However, the Sexual Attractiveness subscale and
the Chest Score of the Body Esteem Scale, which are more relevant to
this population, increase. Although there was a small decrease on the
SF-36, it does not appear to be clinically significant.

No change among Reconstruction patients can be viewed as positive due to
the body image concerns and physical challenges facing these patients.
Nonetheless, a significant improvement in functioning was observed in
the Core Reconstruction cohort, as measured by the Functional Living
Index of Cancer. No change was observed on the Body Esteem Scale,
Rosenberg Self Esteem Scale, or the Mental and Physical Components of
the SF‑36.

The Revision patients represent a uniquely difficult population from
both a medical and psychological perspective; therefore, greater
difficulties, while unfortunate, are not unexpected. Nonetheless, an
increase in the Body Esteem Scale Chest score was observed in the Core
Revision cohort. Many of the other Body Esteem Scale questions are not
relevant for patients with breast implants ([e.g.]{.underline},
satisfaction with feet is one such question). There was no change on the
Rosenberg Self Esteem Scale. Decreases were seen on the SF-36; however,
scores remained high.

The final secondary measure of effectiveness was Global Patient
Satisfaction. Global Patient Satisfaction ratings are frequently used
and widely accepted in outcomes assessments generally, and in plastic
surgery specifically. The satisfaction ratings are compellingly high for
all cohorts and have been maintained throughout the course of the study.

  ----------------------- ----------------------- -----------------------
  **Cohort**              **Two Years**           **Three Years**

  Augmentation            99%                     97%

  Reconstruction          98%                     98%

  Revision                95%                     96%
  ----------------------- ----------------------- -----------------------

These high global satisfaction rates are consistently substantiated in
the literature.

B.  **Correlation Between Satisfaction and Clinical Benefits, As
    Reported in the Literature**

A review of the benefits literature, to be relevant, must focus on more
recent publications, which are more reflective of current cultural
norms. Earlier cultural biases against plastic and reconstructive
surgery are no longer representative of today's implant population.

Self-improvement represents the driving reason for seeking aesthetic
breast augmentation, and women today have highly personal and varied
motives to do so, including: improved body image; improved psychosocial
outcomes (which encompass mental health and well-being generally, and
improved self-esteem, relationships, and sexuality,
specifically).[^40]^/^

With respect to augmentation benefits, satisfaction results are
consistently high in the literature***,*** and correlate to
psychological and physical well-being***.***

-   In an online survey conducted by Young et al. (2004),[^41]^/^ of
    2,273 women who underwent breast augmentation, 98% of the
    respondents reported that the surgery met expectation; 92% reported
    that they were happy with their decision to get implants; 93%
    reported they would recommend the procedure to friends or family;
    and 92% thought that breast augmentation improved their overall
    appearance.

-   The interrelationship of patient satisfaction with improved mental
    and physical well-being was evaluated by Cash et al. (2002), in
    their multicenter, prospective, two-year study in 360 women who
    underwent breast augmentation. They found that overall surgical
    satisfaction with outcome was high, and this satisfaction was highly
    related to improved body image satisfaction (p\<0.001), improved
    self-image (p\<0.001), and improved sexual satisfaction
    (p\<0.001).[^42]^/^

-   In an editorial response to the Cash et al. (2002) article, Sarwer
    noted that: "\[s\]tudies will help correct the public perception
    that cosmetic surgery is simply trivial vanity and will help
    reassure the individual patient that improving one's appearance can
    result in psychological improvements."[^43]^/^

As with the literature, the FDA has acknowledged that "the potential
psychological benefits" offered by silicone gel-filled breast implants
"are an important part of the device's efficacy."[^44]^/^

In addition to psychological benefits of breast augmentation, there are
also functional ([i.e.]{.underline}, restorative) benefits to breast
implants. To better understand these functional/restorative benefits,
the population of cosmetic breast implant recipients must first be
understood. Women seeking breast implants for cosmetic purposes are
predominantly married (64%) and in their 20s, 30s, and 40s; 64% percent
of the married women have children.[^45]^/^ In this population, some
level of breast involution and/or sagging can result from pregnancy,
lactation, and/or significant weight change caused by these events. For
these women, physiological replacement of the involuted/sagging breast
\-- that is, regaining the breast size/shape these women had before
pregnancy, lactation, or weight changes \-- also factors into decisions
for seeking cosmetic breast augmentation.[^46]^/^ Women who have
augmentation for this reason report high levels of satisfaction with the
results of their surgery.[^47]^/^ Thus, there are clearly identifiable
functional ([i.e.]{.underline}, restorative) as well as psychological
benefits to these women.

With respect to breast reconstruction, women seek this procedure for a
variety of reasons related to improved mental health. For example, in a
review of the literature conducted by Harcourt and Rumsey
(2001),[^48]^/^ it was noted that the motivation for breast
reconstruction includes: maintained feelings of femininity, restored
symmetry, improved self-confidence, and avoidance of the need for
external prosthesis.

The clinical benefits of breast implants to women undergoing
reconstruction following mastectomy, are virtually self evident. The FDA
has acknowledged these benefits for over a decade, when it formally
recognized the public health need for these products in the
reconstruction population.[^49]^/^ Clinical benefits of breast implants
in these women also have been reported by several investigators.

-   Significant improvements in all psychosocial variables, including
    emotional well-being, vitality, general mental health, and body
    image were reported by Wilkins et al. (2000) in a large prospective,
    multicenter study that employed validated assessments (Medical
    Outcome Study Short Form-36 (SF-36); Functional Assessment of Cancer
    Therapy-Breast (FACT-B)) to measure these endpoints.[^50]^/^

-   Girotto et al. (2003) conducted a prospective study in which they
    found that older patients ([i.e.]{.underline}, \>65 years of age)
    who elected breast reconstruction, had better outcomes than
    age-matched general population patients and previously reported
    mastectomy-only patients in all surveyed areas ([i.e.]{.underline},
    physical and emotional well-being, social functioning, vitality, and
    general health).[^51]^/^

In conclusion, regardless of study design, the composite of recent
literature consistently demonstrates that satisfaction correlates to
psychological and physical well-being \-- [i.e.]{.underline}, clinical
benefits. Importantly: (1) in a number of the studies, sample sizes
ranged from several hundred to over two thousand; (2) the studies
measuring pre- and postoperative status used the same assessment
instruments; (3) patients served as their own control and were evaluated
using pre- and postoperative assessments; (4) a number of the studies
were multicenter; (5) the majority of studies did not exclude
participants with adverse outcomes; (6) most of the survey instruments
are generally accepted and validated outcome measures; (7) the duration
of studies are representative of social sciences literature; and (8)
satisfaction results are consistent among cited studies and with the
Core Study.

Given these findings, patient and literature reports of clinical
benefits should be factored into the risk/benefit evaluation of Mentor's
silicone gel-filled breast implants

VI. **CLARIFICATIONS OF FDA QUESTIONS PRESENTED TO PANEL**

FDA notes in its question #5 concerning whether there is reasonable
assurance of safety for these devices that "revision patients \[are\] a
continuum for patients originally undergoing breast augmentation or
reconstruction." In Mentor's Core Study, only 3% of augmentation
patients and 7% of reconstruction patients underwent explantation with
replacement. The decision of whether or not to undergo a revision
procedure with implant replacement is a new decision that is ultimately
the patient's choice. At the point of this decision, the patient and her
physician can evaluate the risk/benefit profile for the various revision
options (that may include other alternatives), and determine which, if
any, option to pursue. The decision to pursue revision with implant
replacement is by no means automatic and thus revision patients should
not be viewed as a continuum for all augmentation and reconstruction
patients.

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[^5]: / Berner, I., M. et al. 2002. Comparative examination of
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[^6]: / Gaubitz, M., C., et al. 2002. Silicone breast implants:
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[^7]: / Brown, S.L., et al. 2001. Silicone gel breast implant rupture,
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[^8]: / Fryzek, J.P., et al. 2001. Self-reported symptoms among women
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[^9]: / Wolfe, F. and J. Anderson. 1999. Silicone filled breast implants
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[^10]: / Jacobson, D.L., et al. 1997. Epidemiology and estimate
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[^11]: / Wolfe, F., et al. 1995. The prevalence and characteristics of
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[^12]: / Mancini, G.J., et al. 2002. Parastomal pyoderma gangrenosum: a
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[^13]: / Jacobson, D.L., et al. 1997. Epidemiology and estimate
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[^14]: / Kjøller, K., et al., 2004. Self-reported musculoskeletal
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[^15]: / Hölmich, L.R., et al. 2003. Self-reported diseases and symptoms
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[^16]: / Brown, S.L., et al. 2002. An association of silicone-gel breast
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[^17]: / Berner, I., 2002. Comparative examination of complaints of
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    *Eur. J Obstet. Gynecol. Reprod. Biol.* 102:61-66.

[^18]: / Gaubitz, M.,. 2002. Silicone breast implants: correlation
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    estimated silicone presence in the liver, antibody status and
    clinical symptoms. *Rheumatology* 41(2):129-35.

[^19]: / Fryzek, J.P., et al. 2001. Self-reported symptoms among women
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[^20]: / Park, A.J., et al. 1998. Silicone gel-filled breast implants
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[^21]: / Gilatay, E.J., et al. 1994. Silicone breast prostheses and
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[^22]: / Wells, K.E., et al. 1994. The health status of women following
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[^23]: / Kjøller, K., et al., 2004. Self-reported musculoskeletal
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    Plast. Surg.* 52:1-7.

[^24]: / Hölmich, L.R., et al. 2003. Self-reported diseases and symptoms
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    silicone breast implants. *Plast. Reconstr. Surg*. 111:723-32.

[^25]: / Brown, S.L., et al. 2002. An association of silicone-gel breast
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[^26]: / Berner, I., 2002. Comparative examination of complaints of
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    *Eur. J Obstet. Gynecol. Reprod. Biol.* 102:61-66.

[^27]: / Gaubitz, M.,. 2002. Silicone breast implants: correlation
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    clinical symptoms. *Rheumatology* 41(2):129-35.

[^28]: / Fryzek, J.P., et al. 2001. Self-reported symptoms among women
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[^29]: / Park, A.J., et al. 1998. Silicone gel-filled breast implants
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[^30]: / Wells, K.E., et al. 1994. The health status of women following
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[^31]: / Henriksen, T.F., et al. 2003. Incidence and severity of
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[^32]: / Bondurant, S., V.L. Ernster and R. Herdman, Eds. 2000. *Safety
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[^33]: / Kulmala, I., et al. 2004. Local complications after cosmetic
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[^34]: / [Id]{.underline}.

[^35]: / Hölmich, L.R., et al. 2003. Self-reported diseases and symptoms
    by rupture status among unselected Danish women with cosmetic
    silicone breast implants. *Plast. Reconstr. Surg*. 111:723-32.

[^36]: / [Id]{.underline}.

[^37]: / [Id]{.underline}.

[^38]: / Henriksen, T.F., et al. 2003. Incidence and severity of
    short-term complications after breast augmentation. *Ann. Plast.
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    cohort).

[^39]: / Hölmich, L.R., et al. 2004. Untreated silicone breast implant
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[^40]: / Cash, T.F., et al. 2002. Women's psychosocial outcomes of
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    V.L., et al. 2004. Initial results from an online breast
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[^41]: / Young, V.L., et al. 2004. Initial results from an online breast
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[^42]: / Cash, T.F., et al. 2002. Women's psychosocial outcomes of
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[^43]: / Sarwer, D.B., 2002. Women's psychosocial outcomes of breast
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[^44]: / 64 [Fed]{.underline}. [Reg]{.underline}. 45155 at 45159 (Aug.
    19, 1999) (final rule calling for PMA review of silicone gel-filled
    breast implants, emphasizing in particular, the potential
    psychological benefits offered by these devices).

[^45]: / Young, V.L., et al. 2004. Initial results from an online breast
    augmentation survey. Aesthetic Surgery Journal 24(2):117-35.

[^46]: / [See]{.underline}, [e.g.]{.underline}, Goin, J.M., and Goin,
    M.K. 1981. [Changing the Body: Psychological Effects of Plastic
    Surgery]{.underline}. Baltimore, MD: Williams & Wilkin; Young, V.L.,
    et al. 2004. Initial results from an online breast augmentation
    survey. Aesthetic Surgery Journal 24(2):117-35.

[^47]: / [Id]{.underline}.

[^48]: / Harcourt, D., and Rumsey, N. 2001. Psychological aspects of
    breast reconstruction: a review of the literature. J. Advanced
    Nursing 35(4):477-87.

[^49]: / [See]{.underline} 1992 Adjunct Study Agreement between Mentor
    Corporation and the Food And Drug Administration to Extend Review
    Period for PMAs . . . for Use of the Device in Women with Breast
    Reconstruction, stating "\[t\]he agency has determined that, for
    women seeking breast reconstruction, continued availability of
    silicone gel-filled breast prostheses is necessary for the public
    health" (at 3).

[^50]: / Wilkins, E.G., et al. 2000. Prospective analysis of
    psychosocial outcomes in breast reconstruction: one-year
    postoperative results from the Michigan breast reconstruction
    outcome study. Plast. Reconstr. Surg. 106:1014-25.

[^51]: / Girotto, J.A., et al. 2003. Breast reconstruction in the
    elderly: preserving excellent quality of life. Ann. Plast. Surg.
    50:572-8.