A growing dilemma - breast cancer and pregnancy

Abstract

Breast cancer and pregnancy are events that have an enormous impact on the lives of women. When these events are associated they become a highly emotive issue with possible devastating consequences.
While information on breast cancer is widely available, much less is reported on the association between breast cancer and pregnancy. This article reviews the available evidence on which general practitioners can base their management of women with gestational breast cancer or breast cancer survivors who may want to conceive.
Breast cancer can be diagnosed during pregnancy or in the 12 months postpartum (including lactation), known as gestational breast cancer or pregnancy associated breast cancer. Previous treatment for breast cancer may have detrimental effects for women who subsequently conceive or wish to conceive. General practitioners, as the primary care giver, have an integral role in the successful education, management and support of these women.

Full text

B
reast cancer and pregnancy are
events that have an enormous
impact on the lives of women. An associ-
ation between breast cancer and
pregnancy is uncommon, but can have
devastating consequences. The associa-
tion is likely to become more frequent as
childbearing practices change, and more
women choose to delay pregnancy until
their late 30s and 40s, when the incidence
of breast cancer begins to increase. A
diagnosis of breast cancer can affect
pregnancy in two ways. The first is when
a woman is diagnosed with breast cancer
during pregnancy or in the 12 months
postpartum (including lactation), known
as gestational breast cancer (GBC) or
pregnancy associated breast cancer. The
second is the effect a prior diagnosis of
breast cancer may have on women who
subsequently conceive or wish to con-
ceive. General practitioners play an
integral role in the successful manage-
ment and support of these women both
in the early detection of breast cancer,
education of their patients, and prompt
referral to a specialist tertiary centre.
Historically the association of breast
cancer and pregnancy was thought to
carry a poor prognosis. Gross stated in
1880: ‘(that) its growth is wonderfully
rapid and its course extremely
malignant.’1,2 This negative view, and the
fact that most practitioners’ experience of
GBC is limited, has continued to impact
upon the medical psyche. Most surgeons
and GPs still think the outcome for GBC
is very poor.1Breast cancer survivors
have also been advised against subse-
quent pregnancy as it was thought the
hormonal stimulation would lead to a
worse breast cancer outcome.
Gestational breast cancer
Incidence and outcomes
The reported incidence of GBC ranges
from 0.7-3.8% of all diagnosed breast
cancers.3-7 Overall the incidence appears
low, but as it only affects premenopausal
women the true incidence of GBC is
reported to be between 7-14% of pre-
Australian Family Physician Vol. 31, No. 10, October 2002 •1
CLINICAL PRACTICE: Clinical update
A growing dilemma - breast
cancer and pregnancy
Angela Ives, MSc, is Research Associate, WA Safety and Quality of Surgical Care
Project, Centre for Health Services Research, The School of Population Health, The
University of Western Australia.
James Semmens, MSc, PhD, is Co-Director and Coordinator, WA Safety and Quality
of Surgical Care Project, Centre for Health Services Research, The School of
Population Health, The University of Western Australia.
Christobel Saunders, MBBS, FRCS (Gen Surg), is Associate Professor, University
Department of Surgery, Royal Perth Hospital, Western Australia.
Phillip Puckridge, MBBS, is Registrar, Department of General Surgery, Sir Charles
Gairdner Hospital, Western Australia.
BACKGROUND Breast cancer and pregnancy are events that have an enormous impact
on the lives of women. When these events are associated they become a highly emotive
issue with possible devastating consequences.
OBJECTIVE While information on breast cancer is widely available, much less is reported
on the association between breast cancer and pregnancy. This article reviews the
available evidence on which general practitioners can base their management of women
with gestational breast cancer or breast cancer survivors who may want to conceive.
DISCUSSION Breast cancer can be diagnosed during pregnancy or in the 12 months
postpartum (including lactation), known as gestational breast cancer or pregnancy
associated breast cancer. Previous treatment for breast cancer may have detrimental
effects for women who subsequently conceive or wish to conceive. General
practitioners, as the primary care giver, have an integral role in the successful
education, management and support of these women.

menopausal breast cancers.2,8,9 In the
Australian population this means approx-
imately 200 women per year are
diagnosed with GBC.
Gestational breast cancers have been
shown to have a worse prognosis and are
more advanced at presentation (larger
tumours and lymph node positive) than
nongestational breast cancers.10-13
However, when age and stage are taken
into account there is no difference in sur-
vival between gestational and
nongestational breast cancers. Ezzat
reports a seven year overall survival for
GBC of 57% (95% CI: 33-81) and for non-
GBC 61% (95% CI: 47-75), which was not
statistically significant (P=0.86).2,14,15
Investigation
Although GBCs are generally more
advanced at presentation than non-GBCs
it is unlikely this is due to a differing
behaviour of the disease. The main
reason for worse outcomes in GBC has
been reported to be due to delays in diag-
nosis. The likely reason for this delay is
that abnormalities detected in the preg-
nant or lactating breast by the patient or
clinician are thought to be due to hor-
monal changes and nothing more sinister.
Overall, the literature demonstrates a
delay in investigation of 2-15 months
from the first appearance of symptoms to
confirmed diagnosis in GBC than in their
nonpregnant counterparts.2,3,5,6,12,15,16
General practitioners can play an impor-
tant role in the early detection of GBC by
promoting breast awareness in their pre-
menopausal patients and by prompt and
appropriate referral of pregnant and lac-
tating women with breast abnormalities.
Any breast abnormality found in a
pregnant or lactating woman should be
investigated, in the same way as the non-
pregnant woman, by triple assessment -
clinical assessment, imaging and tissue
biopsy. The physiological changes in the
pregnant or lactating breast may mask the
appearance of a lump, but it is inappropri-
ate to delay investigation on the basis that
the abnormality may be related to preg-
nancy or lactation.1,17,18 The differential
diagnosis of breast symptoms in preg-
nancy are outlined in Table 1. Only breast
lumps that are benign by all three arms of
assessment, can be safely observed.
There are some difficulties with
assessing the pregnant/lactating breast.
Fine needle aspiration cytology is more
difficult to interpret because of cellular
changes within the pregnant or lactating
breast.19 Core biopsy may give more accu-
rate information, but it is more invasive
and there is a small risk of developing a
milk fistula.20-22 It is important for all clini-
cians to clearly specify on pathology
requests that the woman is pregnant or
lactating, to allow the most accurate
appraisal of the specimen.
Medical imaging of the breast during
pregnancy is safe as long as guidelines are
followed. The exposure of the fetus to
radiation should be minimised, and initial
mammography is considered safe, if
abdominal lead protection is used.21,23
Mammography is not always diagnostic in
young women because of the denseness
of the breast tissue, and when pregnant or
lactating this denseness is heightened.21,24,25
With improved imaging quality and tech-
niques this may become less of an issue in
the future. Ultrasound may give equiva-
lent information, or indeed more accurate
information of the breast, with as yet no
known ill effects to the fetus.21,23
Pathologically there are probably no
discernable differences in tumour type
between gestational and nongestational
breast cancer. A large proportion of node
positive GBCs are found at the time of
surgery, with most series reporting
approximately 70% as node positive -
again an indication of late presenta-
tion.2,26,27 Generally there are similar
incidences of inflammatory cancers in
both gestational and nongestational breast
cancer with rates between 1.5-4.0%.11,22,28
Very little research has been carried
out on the histological appearance of
GBCs, but there appears to be no differ-
ence from those in non-GBC.29,30 Larger
studies need to be carried out to provide
conclusive evidence of biological differ-
ences between gestational and
nongestational cancers.
Management
Initial management of GBC is best accom-
plished in a tertiary referral centre where a
multidisciplinary approach can be utilised
(Table 2). This team should not only
include those treating the breast cancer but
those involved in the care of the pregnancy
so that both mother and child have the best
chance of survival. The preferred surgical
treatment of breast cancer during preg-
nancy is mastectomy. Breast conserving
surgery and postoperative radiotherapy,
which is the routine treatment for breast
cancer, is largely contraindicated during
pregnancy. This is because radiotherapy to
the breast, chest wall or axillary lymph
nodes cannot safely be carried out during
pregnancy.1When GBC is diagnosed in the
third trimester then radiotherapy can be
performed after the safe delivery of the
child and in lactating women with lactation
ceased before treatment.21
Chemotherapy administered during the
nA growing dilemma - breast cancer and pregnancy
2•Australian Family Physician Vol. 31, No. 10, October 2002
Table 1. Differential diagnosis
of breast symptoms in
pregnancy
• Lactational abscess
• Galactocele
• Enlarging fibroadenoma
• Physiological changes
• Cancer
Table 2. Management of GBC
• Multidisciplinary approach
• During pregnancy:
- surgery, usually mastectomy
recommended
- radiotherapy contraindicated
- chemotherapy, safe after the first
trimester
- hormone therapy contraindicated
• Postpartum:
- normal management of breast
cancer, with cessation of lactation

first trimester results in unacceptably high
levels of fetal abnormality.1,31 During the
second and third trimester chemotherapy
can safely be given (a malformation rate of
4% is reported - similar to the 3% risk
during a normal pregnancy), although it
may be associated with low birth weight
and early delivery.32,33 There are specific
agents that should be avoided as treatment
during pregnancy including antimetabo-
lites such as methotrexate.34 To date, long
term follow up has demonstrated normal
growth and development of children
exposed to antineoplastic agents in utero.
As yet no clear evidence has supported the
concern of delayed malignancies or infer-
tility developing in these children.
The question arises in GBC whether ter-
mination of pregnancy should be a
management option. In the past, termina-
tion has been the only option given to some
women, but there is no evidence to demon-
strate a survival benefit. Some studies have
shown that termination of pregnancy can
make the breast cancer prognosis worse.10
These results may however, be biased, as it
is possible that women with more advanced
disease or poorer prognostic features were
recommended for termination of pregnancy,
and these women would have a decreased
chance of survival with or without termina-
tion. 20,21 In the 21st century when breast
cancer can be managed safely during preg-
nancy, a women choosing to continue her
concurrent pregnancy can do so with
minimal concern for the child’s wellbeing.
As Byrd succinctly said in 1968: ‘In the face
of general enthusiasm for terminating the
pregnancy, we believe the evidence is that
the cancer should be terminated.’16
Termination of the pregnancy may be
medically indicated in women who
present with advanced breast cancer very
early in the pregnancy when urgent treat-
ment is required.4,21,35 Ultimately women
in this difficult situation, given adequate
information and support, should be able
to make their own informed choice about
their breast cancer management and the
outcome of their pregnancy.
Subsequent pregnancy
Contraception and fertility are two
important issues for premenopausal sur-
vivors of breast cancer. There are many
ways these issues impact on a woman’s
life including the social, psychological,
economic and biological aspects, espe-
cially when their lifespan is potentially
limited.1These important issues require
discussion, but are difficult for practition-
ers to discuss at the time of diagnosis,
especially when there is little evidence on
which to base choices.
Pregnancy is not recommended in the
first two years following treatment.36,37 This
is mainly to ensure the patient does not
develop early recurrence, with its poor
prognosis. Therefore some form of contra-
ception is likely to be necessary but many
clinicians will discourage hormonal contra-
ception. This is because oral contraceptive
pill (OCP) users are known to have a small
increased risk of developing breast cancer
and at present the hormonal effect of OCP
use on any residual tumour following
breast cancer treatment is unknown.23,38
The decision to have a child, planned or
otherwise, is difficult. Questions such as:
• ‘what influence will the pregnancy have
on the breast cancer’
• ‘will my breast cancer recur’, and
• ‘what effect will the breast cancer and its
treatment have on my child’
are likely to arise. Breast cancer survivors
who subsequently conceive have equivalent
survival, and in some studies better survival,
matched for stage than those survivors who
don’t conceive.2,26,27,39-42 This suggests that sub-
sequent pregnancy may provide a survival
benefit, but there may be bias involved, with
only a select group of women, who are gen-
erally healthy going on to become pregnant -
a ‘healthy mother’ effect.43
Fertility
At the other end of the spectrum
chemotherapy can reduce fertility. It has
been estimated that only 7% of fertile
women go on to conceive following a
diagnosis of breast cancer.1,44,45 Many
women who have chemotherapy for
breast cancer will become amennorhoeic,
especially those over 40 years of age.46 In
women with oestrogen receptor positive
tumours, this may account for much of
the beneficial effect of chemotherapy in
breast cancer treatment.31
Infertility can be devastating for the
woman who desperately wants a child.
Various strategies have been proposed to
protect the fertility of a woman undergoing
chemotherapy. These include reversible
chemical sterilisation to protect the follicles
during therapy and cryopreservation of
ovarian tissue but as yet there is no way to
produce an embryo using this tissue.47
Ongoing research in
Australia
There is a project currently underway which
will investigate breast cancer and pregnancy
in the Western Australian population
(Table 3). The WA Record Linkage
System48 will be used to identify women
who were diagnosed with GBC or have sur-
vived breast cancer and subsequently
conceived since 1982. Information will be
gathered on diagnosis, treatment and out-
comes of the breast cancer and pregnancy.
We anticipate this study will lead to a
greater understanding of breast cancer and
pregnancy, and will allow the development
of best practice guidelines on which medical
practitioners can base their management of
these groups of women. It will also provide
information, which will enable women to
make informed choices about their future.
A growing dilemma - breast cancer and pregnancy n
Australian Family Physician Vol. 31, No. 10, October 2002 •3
Table 3. Western Australian Project
• Identify women aged 15-45, diagnosed with GBC since 1982
• Identify breast cancer survivors, aged 15-45, who have subsequently conceived
since 1982
• Gather information on the investigations undertaken and the management and
outcome of breast cancer and pregnancy

Acknowledgments
We would like to thank the Raine Medical
Research Foundation, Perth, Friends of Breast
Cancer Research, Perth, and the NH&MRC
for funding this project.
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nA growing dilemma - breast cancer and pregnancy
4•Australian Family Physician Vol. 31, No. 10, October 2002
CORRESPONDENCE
Ms Angela Ives
Centre for Health Services Research
School of Population Health
The University of Western Australia
Nedlands, WA 6907
Email: iangela@dph.uwa.edu.au