PABC and Treatment options including

Radiation

By: Kelsey Bixler

12-1-14

There are many types of treatments for breast cancer today, but what
about for breast cancer patients who are pregnant? Pregnancy-associated
breast cancer (PABC) is defined as breast cancer that occurs during
pregnancy or within 1 year postpartum. There is much taboo about what
you can or cannot do while being pregnant especially when it comes to
radiation. With this in mind, I think this topic is important to discuss since it is
now popular to delay childbirth, also increasing risk for breast cancer in
various ways because increased age, a lack of breast-feeding and increased
age at first birth increases your risk for breast CA. An important distinction I
want to make is that treating breast cancer while pregnant is very possible
and that termination of a pregnancy is no longer necessary. The set of
references I will use discuss PABC and the risks and special considerations
associated with the disease.
Breast cancer is the most common cancer amongst women in the US
(excluding skin cancer). Common risks associated with breast CA that pertain
to my topic are: increasing age, increasing age at first birth, and lack of
breast feeding. So as the trend continues to move towards childbearing at an
older age, the general risk of breast cancer will increase as would the risk of
PABC. Theres also a relationship between pregnancy and development of
breast CA in general because the breast cancer risk increases transiently
after childbirth but then falls after 15 years.1 Also, pregnancy in general
already increases your short term risk of breast cancer because of the
stimulation of the growth of epithelial cells that have gone through the first

stages of malignant transformation. After delivery, it confers protection by

inducing the differentiation of mammary stem cells which have the potential
for neoplastic change.1 Already being an older woman, this increased risk on
top of your increased age doesnt make an ideal situation. My topics all
agreed that pregnancy was the reason for late diagnosis of many PABC
cases. This late diagnosis would be the reason for advanced disease if the
pregnancy symptoms mask the breast cancer symptoms. Pregnancy causes
multiple changes within the breast, including increased glandularity, size,
and density of the breast tissue, which may obscure a mass.2 These masses
could also be wrongly assumed to be associated with the pregnancy itself.
Also, some studies have found that PABC is commonly diagnosed at
advanced stages because the increased breast density makes clinical exams
and mammograms more difficult to interpret.3 During pregnancy, the
number of mammary epithelial cells increases massively. This proliferation
is accompanied by an increase in angiogenesis and of the number of
stromal cells as well as changes in the extracellular matrix.1 This article also
describes that after lactation, the number of mammary cells decreases
altogether with density due to degradation of the extracellular matrix. In
summary, if pregnancy occurs in a woman who already has breast cancer or
if the cancer occurs during the pregnancy, the number of cancer cells will
consequently increase. This is why early diagnosis is vital and I would think it
would be important to assess the breast well during OB visits.

As you can imagine, the diagnosis of breast cancer during/around the

time of pregnancy represents a challenging treatment scenario. Not only do
you have to safely care for the patient but now you have to consider the
fetus as well. All of my articles agreed that termination of pregnancy is no
longer a necessary option although it is still the patients decision. No doubt,
the planning would be simpler but pregnancy itself does not impart a worse
prognosis.4 In one of my articles, they compared women >35 PABC or nonPABC, data for 668 breast cancers in 652 patients aged 35 years were
retrospectively reviewed. One hundred four breast cancers (15.6%) were
pregnancy-associated; 51 cancers developed during pregnancy and 53 within
1 year after pregnancy. The results of the study showed there were no
differences in locoregional recurrence (LRR), distant metastases (DM), or
overall survival (OS) between PABC and non-PABC patients with similar
treatment or between the two PABC groups (breast cancer during pregnancy
or diagnoses those within the year after).4 Another article stated similar
conclusions in their study saying that the PABC tumors had worse biological
features but was not found to be an independent predictor of worse or
overall survival on multivariate analysis and concluded with therefore,
when women receive timely standard therapy regimens there appears to be
no significant difference in outcomes.2 You can deliver a healthy baby and
have similar survival rates with PABC without having to terminate.
As you now know, there are still many ways to treat breast cancer
while protecting the new critical structure inside of the mother.

Mastectomy was mentioned a lot in articles written earlier, but latter articles
stated that even that might be excessive compared to other options. An
article said that they reported similar survival rates between patients treated
with breast-conserving surgery and those treated with mastectomy.3 Some
considerations in choosing treatment techniques would be stage,
characteristics of the disease, trimester, and overall least risk to the fetus.
Surgery is a feasible option in any trimester. Sentinel node biopsy was
frowned upon in earlier articles but the latest article discussed how it was
widely agreed that sentinel node biopsy for staging of the regional lymph
nodes can be performed safely during pregnancy.3 This was because it was
found that the radioisotope injected remains trapped at the injection site on
the breast or within the lymphatics and that a very small amount of the
injected activity is circulating the blood pool and excreted by the urinary
system, confirming that the level of radioactivity in the body is absolutely
negligible at each time point studied after the administration, proving that
there is a negligible risk to the fetus. All of the articles also said that
chemotherapy is an option after the 1st trimester, systemic treatment with
chemotherapy during the first trimester is associated with a high risk of
miscarriage and in some cases congenital malformations, this being the
period of organogenesis.5 Available data suggests that fetuses exposed to
chemo in the 2nd or 3rd trimester do not experience significant long-term
complications----given that the chemo agents are acceptable during
pregnancy.5,6 Now what about Radiation?

Radiation still seemed a little taboo in these articles. A lot of the

articles mention it but only as an option after the baby has been delivered.
An increased risk of fetal malformation and mental retardation occurs with
radiation doses >10-20 cGy, which wouldnt be reached if the tumors were
located far enough from the uterus with adequate shielding.5 Breast or
thoracic wall radiation exposes the fetus to only 5-15cGy for a regimen of
5000cGy towards the end of pregnancy, the fetus lies closer to the
radiation fields and can receive up to 200cGy for the same protocol1. This
same article gives the maximum dose to the fetus at specific times: 3cGy at
8 weeks gestation, 20cGy at 24 weeks, and 143cGy at 36 weeks. This makes
sense as to why another articles states radiotherapy can be considered
during the first and second trimester but should be postponed during the
third trimester.6 During the 3rd trimester the baby is almost to term and
therefore, takes up a lot of the pelvic/abdominal cavity which is closer to the
breasts. In a couple of the articles, they state that there are many case
reports of normal children born after their mothers had received breast
radiation. One stated, fetal doses ranged from 3.9cGy-18cGy with lead
blocking---without they wouldve received 28cGy.1 Contrary to this,
according to what Ive learned in class and what was stated in my textbook,
the first trimester is the most crucial period, with respect to adverse
consequences from irradiation, and, fetal radiosensitivity decreases as
gestation progresses.7 This makes one even more worrisome for the fetus
when you would need to be treating in that 1st trimester. The Toesca article

had an interesting treatment option called ELIOT (Electron beam

intraoperative radiotherapy). It permits breast radiotherapy in one treatment
and has been used on a phantom to figure the numbers associated with a
pregnant patient. For a total breast dose of 2100 cGy, TLDs showed doses of:
1-85cGy with mean of 37cGy at subdiaphragm, 0.3-2cGy with mean of 9cGy
in the pubic area, and 6-32cGy with mean of 17cGy in utero.3 I think a lot of
the drive away from radiation is because of the unknown risk. I think if there
were more studies done or more ways to prevent fetal dose, that this would
be a more attractive option to PABC patients. I just think its important to
know that it is still an option especially for those with unresectable tumors or
other complications that would result in them delaying treatment.
A lot of my articles had many similarities in treatment options. They all
discussed pros and cons to certain treatments but, the main differences, I
think, had a lot to do with when they were written (2008-2014). The latter
articles would talk about radiation therapy more and options other than
mastectomy. While there is still not a ton of information on this specific group
of people, there is more recent information based on the fact that women are
more often delaying childbearing and because of the fact there needs to be
more research because of this. Some of my articles were written a few years
apart but still had new information leading to more areas of treatment for
this group of women. Theres no doubt that there will be even more
information in the near future regarding this growing group of women. In
conclusion, I would like for my readers to understand that there are definitely

more options today than to have to terminate a pregnancy. Not only that, but
there are more breast conserving options as well. A mastectomy is no longer
the regular treatment option for PABC patients. Potential steps to improve on
research of this topic would be exploring electron or proton therapies,
blocking techniques, or possible ways to make the fetus radioresistant. I
think exploration in these radiation tx modalities could be extremely
beneficial for avoiding high doses to a fetus during radiation treatments. I
think they are definitely worth exploring as this population of people
expands.

References
1. Roman Rouzier, Olivier Mir, Catherine Uzan, Suzette Delaloge,
Emmanuel Barranger, et al. Management of Breast Cancers During
Pregnancy. CNGOF. December 16, 2008.
http://www.cngof.asso.fr/D_TELE/RPC_Ksein_et%20grossesse_en.pdf

2. Litton JK, Theriault RL. Breast Cancer and Pregnancy: Current Concepts
in Diagnosis and Treatment. The Oncologist 2010;15(12):1238-1247.
doi:10.1634/theoncologist.2010-0262.
3. Toesca A, Gentilini O, Peccatori F, Azim HA, Amant F. Locoregional
treatment of breast cancer during pregnancy. Gynecological
Surgery 2014;11(4):279-284. doi:10.1007/s10397-014-0860-6.
4. Beadle, Beth M., Woodward, Wendy A., Middleton, Lavinia P., et. al. The
impact of pregnancy on breast cancer outcomes in women 35 years.
Cancer. 2009; 115(6): 1174-1184.
5. F. A. Peccatori, H. A. Azim, Jr, R. Orecchia, H. J. Hoekstra, N. Pavlidis, V.
Kesic, G. Pentheroudakis, and on behalf of the ESMO Guidelines
Working Group
Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for
diagnosis, treatment and follow-up. Ann. Onc. 2013 24: vi160-vi170.
6. Frdric Amant, Sarah Deckers, Kristel Van Calsteren, Sibylle Loibl,
Michael Halaska, Lieselot Brepoels, et al. Breast cancer in pregnancy:
Recommendations of an international consensus meeting. European
Journal of Cancer. December, 2010. , Volume 46 , Issue 18 , 3158
3168
7. Sherer, M., Visconti, P., et al. Radiation Protection in Medical
Radiography. 7th edition. Maryland Heights, MO. Elsevier; 2014.