Breast Cancer Screening in High-risk Women During Pregnancy and Lactation

Abstract

Women who are at high risk of developing breast cancer warrant screening that is often initiated at younger ages than in average-risk women; this is usually with a combination of annual mammography and breast MRI. Compared to average-risk women, those at high risk are more frequently recommended to undergo screening during childbearing age and thus potentially during pregnancy and lactation. Understanding the appropriate use of screening breast imaging during pregnancy and lactation can be challenging due to limited data defining the evidence-based roles of the different imaging modalities, including mammography, US, and MRI. There have also been assumptions about the diagnostic accuracy of these modalities secondary to physiological changes. This scientific review discusses the current state of evidence- and expert-based guidelines and data for breast imaging screening of high-risk pregnant and/or lactating women, and the clinical and imaging presentations of breast cancer for these women.

Full text

Journal of Breast Imaging, 2023, 1–12
doi:10.1093/jbi/wbad059
Science of Screening
Received: March 30, 2023; Editorial Decision: July 4, 2023
1
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Science of Screening
Breast Cancer Screening in High-risk Women
During Pregnancy and Lactation
Leah H.Portnow, MD,1,2,*, Lauren C.Snider, MD,1
Kimberly E.Bolivar, MD,1 Brittany L.Bychkovsky, MD,2,3,4,5
Margaret R.Klehm, NP, MPH, MSN,5 Eren D.Ye h , MD,1,2,
Eva C.Gombos, MD,1,2 and Sona A.Chikarmane, MD1,2
1Brigham and Women’s Hospital, Department of Radiology, Boston, MA, USA; 2Harvard Medical School, Boston, MA,
USA; 3Dana-Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USA; 4Dana-Farber Brigham
Cancer Center, Breast Oncology Program, Boston, MA, USA; 5Dana-Farber Cancer Institute, Division of Cancer
Genetics and Prevention, Boston, MA, USA
*Address correspondence to L.H.P. (e-mail: lportnow@bwh.harvard.edu)
Abstract
Women who are at high risk of developing breast cancer warrant screening that is often initiated at
younger ages than in average-risk women; this is usually with a combination of annual mammog-
raphy and breast MRI. Compared to average-risk women, those at high risk are more frequently re-
commended to undergo screening during childbearing age and thus potentially during pregnancy
and lactation. Understanding the appropriate use of screening breast imaging during pregnancy
and lactation can be challenging due to limited data defining the evidence-based roles of the dif-
ferent imaging modalities, including mammography, US, and MRI. There have also been assump-
tionsabout the diagnostic accuracy of these modalities secondary to physiological changes. This
scientific review discusses the current state of evidence- and expert-based guidelines and data for
breast imaging screening of high-risk pregnant and/or lactating women, and the clinical and im-
aging presentations of breast cancer for these women.
Key words: screening; high risk; pregnancy-associated breast cancer; pregnancy; lactation.
Introduction
Breast cancer diagnosed during pregnancy or during the rst
postpartum year is dened as pregnancy-associated breast
cancer (PABC). Some sources also include breast cancer
diagnosed during lactation that occursbeyond the rst post-
partum year. Pregnancy-associated breast cancer accounts
for 41% of all malignancies diagnosed during pregnancy
and affects 1 in 3000 women (1). As the age of childbearing
increases and more robust high-risk screening programs be-
come available in the United States and around the world,
breast cancer screening during pregnancy and lactation in
high-risk populations has become clinically pertinent (2,3).
Also, women are now encouraged to breastfeed for up to two
years or longer by the U.S. American Academy of Pediatrics,
increasing the likelihood that there may be breast cancer
screening during lactation (4). Given that patients diagnosed
with breast cancer during pregnancy and lactation typically
have more advanced breast cancer and poorer clinical out-
comes than nonpregnant patients, breast cancer screening
in high-risk women may be especially important for early
detection and diagnosis (5–7). Evidence-based expert recom-
mendations by the American College of Radiology (ACR)
Appropriateness Criteria and the National Comprehensive
Cancer Network (NCCN) provide important guidelines for
screening high-risk women during pregnancy and lactation
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Key Messages
• Breast cancer screening in high-risk women during
pregnancy and lactation is increasingly important be-
cause of later childbearing ages and the establishment
of high-risk screening programs.
• Screening with annual mammography is safe in high-
risk women during pregnancy and lactation and is re-
commended by the American College of Radiology and
the National Comprehensive Cancer Network.
• Screening with contrast-enhanced breast MRI is contra-
indicated during pregnancy but can be performed during
lactation, and non-contrast MRI methods may play a fu-
ture role in screening.
• Further studies, particularly prospective and multi-site
trials, are encouraged to further understand the diag-
nostic performances and outcomes of different imaging
strategies for screening high-risk women.
(8,9). However, there are also a variety of mixed opinions and
conclusions in the literature on this topic. Screening mam-
mography use may be questioned due to the perceived radi-
ation risk to the fetus during pregnancy (7,10). Furthermore,
the value of high-risk screening using breast imaging during
pregnancy and lactation may be questioned due to limited
data in this population and the assumptions about reduced
sensitivity for cancer detection amidst physiological breast
changes of ductal and lobular growth during pregnancy until
involution within three months following lactation cessation
(7,10,11). These physiological changes result in potential in-
creased breast volume, broglandular tissue, and breast den-
sity (6,10). This scientic review discusses the current state
of guidelines and evidence for breast imaging screening of
high-risk pregnant and/or lactating women.
High-risk Women
Women who have a 20% or greater lifetime risk of devel-
oping breast cancer are typically categorized as high-risk.
Risk models such as Gail or Tyrer-Cuzick vary in the variables
used in calculations of risk of developing breast cancer, but
many factors are known to increase risk. These include ge-
netic predisposition, prior chest or mantle radiation therapy
between the ages of 10 and 30 years (cumulative dose of
10 Gy or greater), prior history of breast cancer treated with
breast-conserving therapy at or before the age of 50 years, a
strong family history of breast cancer, and a history of high-
risk lesions (9,12). Approximately 5% to 10% of all breast
cancers are attributed to genetic predispositions (13–17).
Pathogenic or likely pathogenic variants (PVs) in BRCA1
and BRCA2 are the most common cause of hereditary breast
cancer and result in a >60% lifetime risk (18). BRCA1 PV
carriers have a 3.8% annual risk for developing breast
cancer during their reproductive years from the age of 25 to
40 years (19–21). In fact, 11% to 30% of women diagnosed
with PABC are found to harbor a PV in BRCA1 (1,5,22).
Though the incidence of PABC because of non-BRCA PVs
is understudied, other known cancer genetic predisposition
syndromes conferring a high risk of developing breast cancer
at younger ages include TP53-associated Li-Fraumeni syn-
drome (lifetime risk >60%), PTEN-associated Cowden syn-
drome (40%–60%), CDH1-associated hereditary diffuse
gastric cancer (41%–60%), STK11-associated Peutz-Jeghers
syndrome (32%–54%), PALB2 (41%–60%), BARD1
(20%–40%), RAD51C/D (20%–40%), NF1 (20%–40%),
CHEK2 (20%–40%), and ATM (20%–40%) (18,23). High-
risk screening recommendations for these patients vary
depending on the gene but generally include both annual
mammography and annual MRI surveillance based on the
NCCN guidelines (18). Breast MRI may begin as early as 25
years (for BRCA) and as late as 40 years (for BARD1 and
RAD51C/D), or at 10 years prior to the age of the youngest
family member at diagnosis (18). For TP53 PVs, breast MRI
surveillance should begin even younger, as early as 20 years
(18). Initiation of annual mammography may begin as early
as 30 years and as late as 40 years (9,21), depending on the
genetic risk and other risk factors (18,23).
Breast Cancer Screening Methods for
High-risk Women During Pregnancy and
Lactation
A summary of the current ACR and NCCN guidelines for
breast cancer screening in this patient population is shown
in Table 1. A summary of other literature conclusions on this
topic is shown in Table 2. The guidelines used at our institu-
tion are shown in Table 3.
Clinical Breast Examination
Recommendations regarding the use and value of clinical
breast examinations (CBEs) are varied, but NCCN guide-
lines recommend a CBE in high-risk women every 6 to 12
months, starting at the age of 25 years, including during preg-
nancy and lactation (9). In high-risk women, CBE has been
reported to have a high negative predictive value, and a pal-
pable area of concern by clinical or self-breast examination
to have a malignancy rate of 6.7% (24). However, Roeke et
al performed a 7-study systematic review of CBE in this pop-
ulation and suggested that expert consensus reconsider the
role of CBE in screening high-risk women, as its additional
malignancy detection yield was minimal or absent (25). In
a systematic review of the literature regarding screening
during pregnancy and lactation by Zha et al, 12 of the 16
included publications recommended CBE during pregnancy
and 6 recommended CBE during lactation (3,11,19,26). The
recommendations regarding frequency of CBE during preg-
nancy varied between three and six months. For lactation,
the recommendations varied from only at the initial post-
partum visit to every three to six months throughout breast-
feeding (19,26). However, the publications reviewed by Zha
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3Journal of Breast Imaging, 2023, Vol. XX, Issue XX
Table 1. Summary of Current Guidelines for Breast Cancer Screening in Asymptomatic Pregnant and Lactating Women at High Lifetime Risk
Combined ACR Appropriateness Criteria (8) and NCCN Current Guidelines (9,18)
Surveillance Before Pregnancy During Pregnancy During Lactation
Clinical breast
exam
Recommended Recommended Recommended
Once every 6–12 months, beginning as early as 21 years Once every 6–12 months Once every 6–12 months
Screening
mammography
Recommended Recommended Recommended
Annual screening FFDM or DBT, begin earliest at 30 years Annual screening FFDM or DBT
for the following cohorts:
Annual screening FFDM or DBT, any risk level
- 30 years or younger at high
risk
- 30–39 years at intermediate or
high risk
- 40 years or older, any risk
level
Whole-breast US
screening
May be appropriate May be appropriate May be appropriate (8)
Recommended if unable to tolerate MRI Not recommended (9)
DCE-MRI Recommended Contraindicated May be considered in lactating women at high lifetime risk
for breast cancerAnnual DCE-MRI surveillance in adjunct with annual screening
mammography, preferably alternating every 6 months If breastfeeding for a short period of time (<6 months),
resume DCE-MRI 3 months after breastfeeding cessationBegin earliest at 25 years, latest 40 yearsa
Abbreviations: ACR, American College of Radiology; DBT, digital breast tomosynthesis; DCE, dynamic contrast enhanced; FFDM, full-eld digital mammography; NCCN, National
Comprehensive Cancer Network.
aFamily history of breast cancer informs age at initiation of breast cancer screening with mammogram and breast MRI, and for some patients it may be appropriate to start at younger ages.
When our high-risk patients are not pregnant or lactating and are undergoing annual breast MRI and annual mammogram, we alternate between the two imaging modalities every 6 months.
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Table 2. Examples of Other Conclusions in the Literature Regarding Breast Cancer Screening in Asymptomatic Pregnant and Lactating Women at High Lifetime Risk
Surveillance
Before
Pregnancy During Pregnancy During Lactation
Clinical breast
exam
Every 6 months
(19).
Every 3–6 months throughout pregnancy
and/or lactation (6,19,26,37)
Every 3–6 months throughout pregnancy and/or lactation (19,26,37)
Not recommended
(25)
Screening
mammography
Literature consensus is against asymptomatic
screening mammography (3,6,19,35,37)
If 30 years or older and plan to breastfeed less than 6 months, resume
screening mammography 6–8 weeks to 3 months after cessation (6,19,37)
If 30 years or older and plan to breastfeed longer than 6 months, resume
screening mammography within the rst 6 months postpartum (19)
Whole-breast US
screening
Not recommended
(19)
Not performed if asymptomatic (3,19)Not recommended if asymptomatic (19)
Every 3 months during pregnancy and
lactation (37). Every 3 months during pregnancy and lactation (37).
DCE-MRI Contraindicated (1,3,6,10,19,37)If plan to breastfeed less than 6 months, resume either screening
mammography or surveillance DCE-MRI 6–8 weeks after cessation
(3,19)
If plan to breastfeed longer than 6 months, resume DCE-MRI within the
rst 6 months post-delivery (3,19)
Limit breastfeeding to 6 months and resume DCE-MRI at 6 months
postpartum (37).
Abbreviations: ACR, American College of Radiology; DCE, dynamic contrast enhanced; NCCN, National Comprehensive Cancer Network.
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5Journal of Breast Imaging, 2023, Vol. XX, Issue XX
Table 3. Our Institution Guidelines for Breast Cancer Screening in Asymptomatic Pregnant and Lactating Women at High Lifetime Risk
Surveillance Before Pregnancy During Pregnancy During Lactation
CBE Recommended Recommended Recommended
Two CBEs per year to coincide with breast
imaging schedule
Continue 2 CBEs per year and
continue CBE during pregnancy
Continue 2 CBEs per year to coincide with
postpartum breast imaging schedule
Screening mammographyaBRCA1, BRCA2, CDH1, NF1, PALB2, STK11,
TP53: Begin annual FFDM or DBT at 30
years
Not performed Resume annual screening FFDM or DBT at ~9
months post-delivery, performed at least 6 months
following initial early lactation period DCE-MRI
PTEN: Begin annual FFDM or DBT at 35 years
ATM, BARD1, CHEK2, RAD51C, RAD51D:
Begin annual FFDM or DBT at 40 years
High-risk, but breast cancer risk gene–negative:
per shared decision making
Whole-breast US screening Not performed Not performed Not performed
DCE-MRIaTP53: Began annual DCE-MRI at 20 years Contraindicated Resume annual surveillance DCE-MRI 2–4 months
post-delivery followed by annual screening
mammography 6 months thereafter
BRCA1, BRCA2: Begin annual DCE-MRI at
25 years
CDH1, NF1, PALB2, STK11: Begin annual
DCE-MRI at 30 years
ATM, CHEK2: Begin annual DCE-MRI at
30–35 years
PTEN: Begin annual DCE-MRI at 35 years
BARD1, RAD51C, RAD51D: Consider annual
DCE-MRI at 30–35 yearsb
High-risk, breast cancer risk gene–negative: per
shared decision making
Abbreviations: ACR, American College of Radiology; CBE, clinical breast exam; DBT, digital breast tomosynthesis; DCE, dynamic contrast enhanced; FFDM, full-eld digital mammography;
NCCN, National Comprehensive Cancer Network.
aFamily history of breast cancer informs age at initiation of breast cancer screening with mammogram and breast MRI, and for some patients, it may be appropriate to start at younger ages.
When our high-risk patients are not pregnant or lactating and are undergoing annual breast MRI and annual mammography, we alternate between the two imaging modalities every six months.
bThis recommendation differs from current NCCN guidelines, which recommend starting breast MRI at 40 years for women with BARD1, RAD51C, and/or RAD51D pathogenic variants. This
recommendation is based on expert consensus at our institute to consider starting breast MRI for screening in this patient population prior to 40 years. As part of shared decision making, we
consider the patient’s willingness to start screening between the ages of 30 and 35 years and their family history of cancer.
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6Journal of Breast Imaging, 2023, Vol. XX, Issue XX
et al were predominantly a compilation of expert opinion,
systematic reviews, and anecdotal evidence; no signicant
primary literature was included (3). Ultimately, their overall
conclusion was to recommend CBE for high-risk breast
cancer screening because of its safety prole and high speci-
city (3). However, it is known that CBE can be challenging
during the gravid and postpartum periods (3,27). Additional
studies would be helpful to clarify the role of CBE in the
high-risk population during pregnancy and lactation.
Mammography
During Pregnancy
The ACR guidelines for breast cancer screening during preg-
nancy indicate that initial imaging with either full-eld dig-
ital mammography (FFDM) or digital breast tomosynthesis
is “Usually Appropriate” for patients younger than 30 years
who are considered high-risk, patients aged 30 to 39 years
who are considered intermediate- or high-risk, and patients
aged 40 years or older at any risk level (8). The NCCN also
provides guidelines for breast cancer imaging screening
during pregnancy and recommends that women at increased
risk who are pregnant undergo CBE and annual screening
mammography (9).
There is no contraindication to performing mammog-
raphy during pregnancy or lactation. However, the perceived
radiation dose risk to the developing fetus has been a barrier
to its use (19). In fact, the absorbed fetal dose is negligible—
much lower than the thresholds for teratogenic (50 mGy)
and deterministic effects (100 mGy) (1,6,10,28,29). Current
FFDM absorbed fetal doses are approximately 0.004 mGy
(1,6,28,29). Patient shielding is not recommended, as most of
the dose to the uterus is from internal scatter radiation, which
is not particularly reduced by shielding (6,30). Additionally,
there is no denitive evidence that there are negative effects
of ionizing radiation on proliferating breast tissue (10).
Overall, the literature is limited regarding the use of
screening mammography in high-risk pregnant women. In
the 16-paper systemic review by Zha et al, 3 of the included
publications specied genetic PVs as the high risk factor and
the other publications did not specify the high-risk factors
(3). Three publications specifying genetic PVs and 1 publi-
cation with an unspecied high-risk factor recommended
against screening mammography in asymptomatic high-risk
women during pregnancy, which contrasts with the current
ACR guidelines (3,8). One of thearticles specically cited
concerns about perceived radiation risk and false positives
in asymptomatic high-risk women (19). Although screening
mammography may be safely performed during pregnancy
in high-risk patients, patient and provider education re-
garding the negligible fetal dose and the potential benets of
screening may be necessary.
During Lactation
The ACR breast cancer screening guidelines for women
who are lactating are the same as for non-lactating women,
whether at average or high lifetime risk (8). The NCCN
guidelines state that there is no contraindication to rou-
tine high-risk screening mammography during lactation
and that women should not delay routine screening be-
cause of ongoing lactation (9). Patients who are lactating
are often encouraged to breastfeed or pump prior to imaging
to potentially decrease breast density and aid detection of
mammographic ndings (6,8,11,31). However, there are no
data indicating that breastfeeding or pumping prior to mam-
mography impacts diagnostic accuracy. It is well known that
dense tissue decreases the sensitivity of mammography from
80% to 60% when compared with non-dense breast tissue,
but emptying the breast will not achieve this amount of den-
sity change (32–34).
In the literature, screening mammography recommenda-
tions in lactating high-risk women are varied (3,6,19,35).
In the work by Zha et al, only 2 of the 4 publications re-
commended high-risk screening with mammography during
lactation. The timing at which to resume high-risk screening
mammography after pregnancy varies in the literature, with
suggestions including after the rst three months, within the
rst six months, or six to eight weeks after breastfeeding ces-
sation if the patient planned to breastfeed for less than six
months (3,6,19,35). Screening mammography during lacta-
tion is safe as it employs a standard low radiation dose.
US
Although diagnostic US is readily accepted as “Usually
Appropriate” for all women, including high-risk pregnant
and lactating patients presenting with clinical signs or
symptoms (6,8,36), recommendations regarding whole-
breast US screening (WBUS) are varied during pregnancy
and lactation (Table 2). The ACR guidelines state that
screening breast US “May Be Appropriate.” It is considered
a second-line modality and an adjunct to mammography
for breast screening in high-risk pregnant women younger
than 40 years, as well as during lactation at any risk level
(8). The NCCN guidelines consider WBUS to be optional in
asymptomatic high-risk pregnant women and advise that
it should performed on a case-by-case basis (9). Concerns
regarding screening WBUS as a supplemental modality
during pregnancy and lactation relate to the low positive
predictive value and relatively high false positive rate (19).
Data regarding use and outcomes of WBUS in the high-risk
pregnant or lactating population are limited. Faermann
et al published a single-institution, retrospective, observa-
tional assessment of screening WBUS in 263 pregnant and/
or lactating Israeli women with BRCA1/BRCA2 mutations
(37). The women underwent surveillance CBE and WBUS
every three months during pregnancy and breastfeeding
(37). Mammography was only performed as a diagnostic
test in women in whom cancer was suspected or conrmed.
Six PABCs were detected with WBUS, 4 of which occurred
during pregnancy and 2 during breastfeeding (37). The pos-
itive predictive values of biopsy were 11% in pregnancy
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7Journal of Breast Imaging, 2023, Vol. XX, Issue XX
and 8% in lactation, which were lower compared with
nonpregnant and non-lactating BRCA PV carriers, in whom
it was 17.6% (38). Although this study demonstrated some
utility of sonography in breast cancer screening, larger
studies should be performed to establish stronger evi-
dence for or against the use of WBUS, especially in light of
stronger evidence for the use of screening mammography
during pregnancy and lactation and for breast MRI in the
postpartum period (39).
MRI
During Pregnancy
Dynamic contrast-enhanced (DCE) MRI is contraindicated
during pregnancy in women of all breast cancer risk levels
according to ACR and NCCN guidelines due to safety
concerns about gadolinium-based contrast agents (8,9).
Intravenous gadolinium is known to cross the placenta and
enter fetal circulation (6,10). This increases the theoretical
risk of gadolinium accumulation in the amniotic uid and
potential dissociation of free gadolinium ions, resulting in
free ion deposition in developing solid organs and neurotox-
icity (1,6,40). A retrospective cohort study evaluating long-
term fetal safety following contrast-enhanced MRI exposure
during pregnancy (n = 397) concluded that DCE-MRI per-
formed at any time during pregnancy, especially during the
rst trimester, conferred an increased risk of long-term rheu-
matological, inammatory, and inltrative cutaneous neo-
natal conditions up to the age of 4 years in early childhood
(31% risk), and also increased the risk of stillbirth or ne-
onatal death (1.7%) (41). For these reasons, DCE-MRI is
contraindicated during pregnancy (8,9).
During Lactation
Dynamic contrast-enhanced MRI for breast cancer screening
can be performed during lactation according to ACR and
NCCN guidelines (10,26). Gadolinium-based contrast agents
are excreted into breast milk at 0.0004% of the rate of the
administered maternal dose over the rst 24 hours, thus less
than 1% of the ingested amount is absorbed by the neo-
natal gastrointestinal tract. The absorbed dose is negligible
to the infant (1). The ACR guidelines do not require breast-
feeding cessation following gadolinium administration given
the negligible amount excreted in breast milk. The American
College of Obstetricians and Gynecologists recommends
non-interruption of breastfeeding post-gadolinium adminis-
tration (42). Per ACR guidelines, patients may elect to pump
and discard breast milk for 12 to 24 hours following gado-
linium administration if that is their preference (43).
The detection of breast cancer on MRI has been perceived
to be more challenging during lactation because of marked
background physiological enhancement (10). However, re-
cent studies demonstrate 98% to 100% sensitivity of breast
MRI in the detection of known, biopsy-proven breast cancers
in lactating women (44–50). Breast cancer has been shown to
have rapid initial enhancement and delayed washout kinetics,
often distinct from lactation-related enhancement patterns
that demonstrate rapid initial enhancement followed by de-
layed plateau enhancement. The evaluation of Myers et al
was that MRI of biopsy-proven PABCs demonstrated greater
disease extent and/or larger tumor size in 12 of 53 patients
(23%), and MRI use led to changes in the surgical manage-
ment of 15 of 53 patients (28%) (45). Studies by Nissan et
al and Oh et al both demonstrated that non-mass enhance-
ment corresponding to biopsy-proven ductal carcinoma in
situ enhanced more avidly than the surrounding lactation-
induced background parenchymal enhancement (46,47). Of
note, as in non-lactating women, MRI evaluation during
lactation may over-estimate tumor size (49). Despite these
studies showing no signicant effect of lactation on diag-
nostic accuracy, some have encouraged lactating patients to
breastfeed or pump immediately prior to undergoing MRI
because it may minimize uid ductal secretions (10). Nissan
et al found that temporary cessation of breastfeeding for one
to two weeks prior to diagnostic MRI signicantly decreased
lactation-induced background enhancement (46). However,
no studies have indicated that these practices improve diag-
nostic accuracy. Current guidelines and experts recommend
resuming MRI surveillance 6 to 12 weeks after breastfeeding
cessation (Table 2). Situations where it is recommended that
MRI be resumed during breastfeeding include if the patient
plans to breastfeed for longer than six months and in unspec-
ied “very high-risk women” (6,8,19).
Contrast-Enhanced Mammography
For high-risk women in whom breast MRI is contraindicated,
the NCCN guidelines state that screening with contrast-
enhanced mammography may be considered, although
there is no current evidence supporting its use in high-risk
screening during pregnancy or lactation (9). Evidence will
continue to emerge. Although not contraindicated during
pregnancy, iodinated contrast can cross the placenta and
enter fetal circulation, with a theoretical risk of disrupted
fetal thyroid development (51). During lactation, a negli-
gible amount of iodinated contrast material is excreted in
the breastmilk, with <0.01% of this absorbed by the infant
gastrointestinal tract (1,8).
Breast Cancer During Pregnancy and
Lactation
Examples of PABCs and their different imaging appear-
ances are shown in Figures 1–3. The classic clinical pres-
entation of PABC is a palpable breast mass (11,36,52).
Less common presentations include focal pain, milk re-
jection from the affected breast during breastfeeding,
bloody nipple discharge, and inammatory changes such
as erythema, skin thickening, and edema, which could be
misdiagnosed as mastitis or an abscess (6,11,52,53). The
rst-line modality to evaluate clinical signs and symp-
toms is diagnostic US (8). The accuracy of targeted US for
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8Journal of Breast Imaging, 2023, Vol. XX, Issue XX
evaluating a palpable mass in this patient population has
been reported to be high, with one study demonstrating
100% sensitivity, 86% specicity, and a positive predic-
tive value of 19% (52). Similar to cancers in women who
are not pregnant or lactating, the classic US appearance of
cancer during pregnancy is an irregular hypoechoic mass
with indistinct or spiculated margins (10,54). US ndings
may also include masses with circumscribed margins, not
parallel or parallel orientation, cystic spaces, and posterior
shadowing or enhancement (10). If a targeted US nding
is suspicious, mammography should be performed ei-
ther before breast biopsy as part of the initial diagnostic
workup or after breast biopsy if the biopsy results con-
rm breast cancer. The mammographic appearances of
PABC include masses, asymmetries, architectural distor-
tions, microcalcications, skin thickening, and/or axillary
adenopathy (10,54). MRI is contraindicated during preg-
nancy but may be performed in the immediate postpartum
Figure 1. Thirty-six-year-old woman with a BRCA1 mutation who, at 15 months postpartum and during lactation, underwent a high-risk
screening breast MRI. Fat-suppressed T1 post-contrast axial (A) and maximum intensity projection reconstruction (B) breast MRI images
demonstrate segmental clumped non-mass enhancement in the left lower outer breast from middle to posterior depth spanning up to
5.6 cm in the anterior-posterior dimension (arrows), in the context of bilateral marked background parenchymal enhancement related to
lactation. C: Kinetic overlay shows mixed enhancement kinetics in the non-mass enhancement, with the red overlay indicating washout
enhancement on the delayed phase (arrows). Subsequent MRI-guided biopsy (not shown) of one of the findings demonstrated invasive
ductal carcinoma and ductal carcinoma in situ, grade II/III, ER+, PR+, and HER2−. The patient underwent surgery, first with bilateral
mastectomy, and the anatomic pathology stage was T1cN0 with 16 distinct foci of invasive disease.
Figure 2. Thirty-four-year-old woman with a BRCA1 mutation at 38 weeks of pregnancy who presented with a palpable area of concern; at
biopsy, this was found to be a triple-negative breast cancer, grade III/III. A: Right breast diagnostic US at the 8-o’clock position, 6 cm from
the nipple, demonstrates a 2.8-cm complex cystic and solid mass (arrow). A partially visualized silicone implant is present. Craniocaudal
(B) and mediolateral (C) silicone implant–displaced diagnostic mammogram views with a triangular shaped palpable marker overlying the
area of concern show a corresponding equal density oval mass with obscured margins (arrows). Axial (D) and sagittal (E) fat-suppressed T1
post-contrast breast MRI images obtained postpartum demonstrate a 1.7-cm oval mass with irregular margins and heterogeneous or rim
internal enhancement (arrows). No other sites of disease were seen. The patient underwent neoadjuvant chemotherapy postpartum, with
complete imaging response to treatment (not shown). She then had bilateral nipple-sparing mastectomies, and the right breast surgical
pathology showed no residual invasive carcinoma but focal ductal carcinoma (pathologic complete response).
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9Journal of Breast Imaging, 2023, Vol. XX, Issue XX
period and when the patient is lactating to assess extent of
disease (8). On MRI, PABC tends to have early and more
intense enhancement than surrounding background paren-
chymal enhancement, similar to cancers in women who
are not pregnant or lactating (10,54). The most common
subtype of PABC is triple-negative breast cancer, which is
often seen in younger women and is more aggressive with
an increased likelihood of tumor necrosis (8,55).
Treatment options for breast cancer are more limited
during pregnancy. Surgical options include breast conserva-
tion with lumpectomy and radiation or mastectomy, with no
difference in survival benet (55). Surgery can be performed
at any time during pregnancy, but general anesthesia carries
a risk of miscarriage (55,56). Because of the requirement for
adjuvant radiation, which is contraindicated in pregnancy,
mastectomy is often preferred if breast surgery is indicated
during the rst trimester (55,56). Reconstruction after mas-
tectomy is often delayed to avoid the risks posed by pro-
longed general anesthesia to the pregnant woman and fetus
(55). If lumpectomy during the rst trimester is pursued, ra-
diotherapy is delayed until the postpartum period, increasing
the potential for local recurrence and/or distant disease (55).
Gestational radiotherapy increases the risk for intrauterine
growth restriction, intellectual disability, and childhood
cancer (57). Systemic chemotherapy deferment to second
and third trimesters is recommended and considered safer
for the developing fetus (55–57). Endocrine therapy and
targeted anti-HER2+ and programmed death ligand-1 im-
munotherapy are contraindicated during pregnancy (55).
The overall survival of patients with PABC when compared
with nonpregnant women matched by age and stage varies
between studies. Some studies demonstrate similar outcomes
and others show poorer outcomes, which may be related to
delays in diagnosis or in the initiation of certain treatments,
including taxanes or HER2-targeted therapies, or to differing
tumor biology and responsiveness to treatment (6,58–63).
Recurrences are high among women with PABC, with local
recurrence reported in 6.5% to 10.9% and distant metastatic
disease reported in 17.4% to 20.8% of PABC patients, which
usually appear within two to three years of diagnosis (58,59).
Future Directions
Non-contrast breast MRI may prove helpful in high-risk
screening for breast cancer detection. Diffusion-weighted
imaging (DWI) in MRI is an unenhanced technique that
measures the microscopic, thermal-induced, random motion
of water and other small molecules within tissue. Diffusion
tensor imaging (DTI) is an advanced MRI technique that
measures water diffusion rates in various directions via ap-
plication of different diffusion gradients (64). The diagnostic
performance of diffusion-based MRI is not limited by back-
ground parenchymal enhancement or by dense breast tissue
(64). Prior studies have demonstrated that breast malignancies
Figure 3. Twenty-nine-year-old female with a BRCA1 mutation who underwent a non-contrast whole-body MRI with diffusion-weighted
imaging (DWI) at 15 weeks’ gestation, following abnormal early second trimester fetal aneuploidy screening indicating maternal
malignancy of unknown origin. A: MRI DWI performed at b1500 sec·mm−2 demonstrates a heterogeneously hyperintense 4.7-cm right
breast mass (arrow). B: Corresponding apparent diffusion coefficient (ADC) at b50 sec·mm−2 shows the mass has hypointense signal
(arrow). Diffusion-weighted imaging at b50 sec·mm−2 (C) also demonstrates hyperintense left axillary lymphadenopathy, with ADC (D) at
b50 sec·mm−2 showing corresponding hypointense signal. Right axillary lymphadenopathy was also present on MRI (not shown), and no
MRI left breast mass was visualized. Palpable masses were subsequently found in both breasts. Right breast mediolateral oblique (MLO)
mammogram (E) demonstrates a spiculated irregular mass with associated fine pleomorphic calcifications in the upper central breast
posterior depth (arrow). Enlarged right axillary lymph nodes are present (arrowhead). Left breast MLO mammogram (F) demonstrates
a focal asymmetry (arrow) with associated architectural distortion, nipple areolar complex involvement, and skin thickening. Enlarged
left axillary lymph nodes are present (arrowhead). Right breast US (G) demonstrates a 4.9-cm irregular hypoechoic mass with indistinct
margins at the 12-o’clock position, 4 cm from the nipple. Left breast US (H) demonstrates a 4.2-cm irregular hypoechoic mass with indistinct
margins at the 12-o’clock position, 2 cm from the nipple. The left breast mass was invasive carcinoma with lobular features, modified grade
III/III, triple-negative. The right breast mass was invasive ductal carcinoma, grade III/III, ER low-positive. Bilateral axillary lymph nodes were
positive for malignancy.
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10 Journal of Breast Imaging, 2023, Vol. XX, Issue XX
exhibit restricted diffusion, as evidenced by DWI hyperintense
signal and apparent diffusion coefcient hypointense signal
relative to the surrounding normal breast parenchyma. A ret-
rospective review by Amornsiripanitch et al demonstrated
that radiologists detected more mammographically occult
malignancies with supplemental DWI than with targeted US
(65). Feasibility studies by Nissan et al showed visualization
of 9 out of 11 known PABCs in pregnant women and 16 out
of 16 known PABCs in lactating women with non-enhanced
DTI. Diffusion tensor imaging parametric maps had superior
contrast-to-noise ratio and, thus, improved tumor conspi-
cuity when compared with conspicuity on contrast-enhanced
sequences with marked background parenchymal enhance-
ment in lactating patients (50,64).
A limitation of diffusion-based imaging is its inferior
spatial resolution relative to contrast-enhanced MRI, which
may impact sensitivity, such as for cancers which present as
small masses or non-mass enhancement (64,66). Diffusion-
based imaging also has a propensity for technical artifacts,
which limits its use (64,66). Additionally, the prone position
is currently required for breast MRI, which is not feasible
for pregnant patients during the third trimester and could
be challenging even during the second trimester. However,
a recent early study showed that breast MRI using the su-
pine technique had adequate technical quality (67). Overall,
MRI techniques such as DWI and DTI show early promise as
complementary tools to other breast imaging modalities in
screening and diagnostic evaluation (46).
Conclusion
Breast cancer screening during pregnancy and lactation
in high-risk women is increasingly important because of
later childbearing ages and the establishment of high-risk
screening programs. Across the ACR and NCCN guidelines
for screening high-risk women during pregnancy and lac-
tation, there are recommendations for CBE every 6 to 12
months, annual mammography, consideration of WBUS
as a supplementary tool, no breast MRI during pregnancy
because of contraindications regarding gadolinium, and re-
sumption of annual breast MRI after pregnancy and poten-
tially during lactation (8,9). Beyond these expert guidelines,
there are varied opinions and conclusions in the literature
regarding the use of these tests for screening in this patient
population. Importantly, mammography is safe with no
contraindications during pregnancy and lactation for high-
risk screening. Further studies, particularly prospective and
multi-site trials, are encouraged to further understand the
diagnostic performances and outcomes of these imaging mo-
dalities for screening high-risk women. Newer non-contrast
MRI techniques are under investigation and may play a fu-
ture role in the detection of PABC.
Funding
None declared.
Conflict of Interest Statement
None declared.
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