SUMMARY OF AN EASY ABOUT PREGNANCY ASSOCIATED BREAST CANCER

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SSuummaarryy
Pregnancy-associated breast cancer (PABC) is defined as any breast carcinoma diagnosed during pregnancy or during the first postpartum year. Breast cancer is one of the most frequently diagnosed malignancies during pregnancy with an incidence of one in 3000 pregnancies.
The diagnosis is difficult and often delayed resulting in later stage presentation due to pregnancy related physiological changes. History taking should stress on risk factors and family history. About 48% of women with an early-onset of breast cancer have a positive family history and 9% were associated with BRCA 1 or BRCA 2 mutations.
Most women diagnosed with pregnancy-associated breast cancer will present with a painless mass in the breast. Palpation cannot discriminate malignant from benign lumps.
Breast ultrasound has a high sensitivity and specificity for the diagnosis of PABC. It can distinguish between cystic and solid breast lesions. It is the standard method for the evaluation of a palpable breast mass during pregnancy.
With adequate abdominal shielding, a mammography presents little risk to the fetus throughout the pregnancy. However, mammography is often less useful than ultrasound in PABC with a significantly higher false-negative. The main role of mammo-

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graphy is to exclude diffuse malignant-type micro-calcifications which would preclude breast-conserving surgery. Digital mammography is more accurate in detecting breast cancer in women aged under 50 years.
MRI may be used in pregnant women if other non-ionising forms of diagnostic imaging are inadequate or if the examination provides important information that would otherwise require exposure to ionizing radiation, but MRI is not recommended during the first trimester because the developing embryo is susceptible to injury from various physical agents.
A core needle biopsy is the technique of choice for histological examination. Fine Needle aspiration cytology (FNAC) may be misleading and should not be performed during pregnancy. The pathologist must be made aware of the pregnancy to avoid misdiagnosis of hyperproliferative changes of the breast during gestation.
Most PABC are invasive ductal carcinomas. A common finding is a high frequency of estrogen-receptor (ER)-negative tumors and patholo-gical lymph node involvement. Some recent studies suggest that HER-2/Neu overexpression and epidermal growth factor receptors to be higher in PABC compared to breast cancer without pregnancy.
Staging in PABC is done according to the usual TNM system of breast cancer. Suspected pulmonary metastases can be

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investigated by chest X-ray with proper using of abdominal shielding, liver ultrasound is the preferred technique to detect liver metastases. Bone scan for searching for bone metastasis is only recommended in cases of uncertain MRI findings, or when MRI is unavailable.
Before medical management physician should be aware of the psychological issue of this especial case of breast cancer. Cancer during pregnancy puts the mother in a difficult situation. Also, for the medical team it is a complex setting, because two individuals are involved: the mother and her unborn child. This require a more a different ways of dealing with our patient than the traditional ones
Good communicating skills are necessary for breaking the bad news. This requires a skilled staff in communication, transparency, shared decision making and avoiding uncertainties. The patient is more satisfied when she is more capable of understanding investigations, prognosis, risks and treatment options. It was believed that by telling the true diagnosis of cancer, doctors would cause additional harm to the patient. Now this way of handling information completely changed. However the information should be given in pieces at several different appointments.
The therapeutic approach to breast cancer during pregnancy requires the participation of a multidisciplinary team. The

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protocol of treatment of breast cancer in pregnant women should be as close as possible to that offered to non-pregnant women. Treatment should be individualised, taking into account the age of pregnancy at diagnosis, the patient’s preferences and stage of the disease. Treatment plan according to the stage of pregnancy can be summerized as follow:
In the 1st trimester, if no indication for termination of pregnancy, mastectomy is done with axillary staging, adjuvant chemotherapy is startred in the 2nd trimester. raditherapy and hormonal treatement if indicated should start only after delivery.
In the 2nd or 3rd trimesterS: mastectomy or conservative surgery cab be done with axillary staging. adjuvant chemotherapy should be started after surgery but adjuvant radiotherapy or hormonal treatement cab be delivered only after delivery. Neoadjuvant chemotherapy cab be considered in some cases during pregnancy only starting from the second trimester.
Survival of pregnant patients with breast cancer is not increased by termination of the pregnancy, even if the cancer has spread. Termination of PABC is only valid if pregnancy itself is an obstacle to drastic treatment, is associated with unacceptable risks for the health of mother and fetus or is thought to be morally unacceptable in the presence of incurable maternal cancer.

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Surgery and anaesthesia are safe during pregnancy if physiologic alterations are considere. Except in the first trimester, pregnancy does not change the indications of the type of surgery, conservative or radical. Breast conservation performed during the first trimester is probably associated with an excessively long delay in postoperative radiotherapy. Conservative surgery at the end of second and third trimester can be proposed and radiotherapy is delayed until after childbirth.
Patients with PABC are excluded from the randomized studies on SLNB. But when the tumor is diagnosed at an early stage, a considerable proportion of patients have node-negative disease and might therefore benefit from SLNB. Because of this controversy,one trial supported the the safety of SLNB in pregnant patients with breast cancer, when performed with a low- dose lymphoscintigraphic technique.
Radiotherapy is contraindicated in pregnancy especially in the second and third trimesters. It should be postponed until after delivery. But in a Patient diagnosed in the first trimester and need to presesrve her breast, then there is the question of giving postoperative radiotherapy before delivery only in 1st or early 2nd trimester, or delaying it until later. Here, the decision should be taken after a thorough discussion of available data between the patient, her family and the multidisciplinary team, taking into account the potential benefits and risks of this treatment.

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Administration of chemotherapy during the first trimester is contraindicated and should be postponed. During the second and third trimester, chemotherapy can be administered relatively safely. Different chemotherapy regimens have been used for the treatment of PABC. Anthracyclines-based regimens are the most widely used is breast cancer treatment and has been shown to be associated with favorable safety profile when administered during pregnancy.
In the advanced/metastatic setting, anthracycline-based regimens remain the best choice as well. For patients who are not good candidates for anthracycline-based regimens, single agent taxane (paclitaxel or docetaxel) would be a preferred option. Weekly administration of paclitaxel has been shown to be associated with higher efficacy and better tolerability compared to the 3-weekly schedule.
Chemotherapy should not be given after 34-35 weeks of gestation as spontaneous delivery can occur before bone marrow recovery. The delay of delivery for 2-3 weeks after chemotherapy also allows for fetal drug excretion via the placenta. Chemotherapy may start again at 10 days postpartum.
Hormonal treatment, if indicated, should be started after delivery and after completion of chemotherapy.
Safety profile of trastuzumab during pregnancy is unclear. Trastuzumab was associated with increase in oligohydramnios

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risk which is known to significantly increase the risk of premature delivery, fetal morbidity and mortality, However, the risk appeared to be much lower in those exposed to trastuzumab for one trimester or less.
Biphophonates have an increase risk of fetal skeletal anomalies secondary to in-utero exposure and can also affect uterine contraction. It is better to administer biphophonates following delivery whenever possible.
Obstetric role in patient with PABC is necessary. Prenatal care should be performed as in a high-risk obstetric unit. Before every cycle of cytotoxic treatment, an evaluation of fetal morphology, growth and wellbeing must be carried out by ultrasound screening. The time of delivery should be balanced according to the need of breast cancer treatment and the maturation of the fetus. Vaginal birth holds a lower risk of maternal morbidity compared with caesarean section.
The prognosis of pregnant women does not seem to differ from that of non-pregnant patients of the same age and stage of disease. It is possible that the worse prognosis initially attributed to pregnant women was due to a more advanced stage at diagnosis or a less standardized therapy
A common question asked by a pregnant lady still under or had finished treatment of a breast cancer is about the feasabilty to breastfeed her baby. Suppression of lactation does not improve

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prognosis. Breast cancer survivors who become pregnant should be encouraged to breastfeed. A history of breast surgery and radiation may affect milk supply. Mothers who have undergone mastectomy but no radiation to the remaining breast can often develop a full supply for one infant. There should be a time interval of 14 days or more from the last chemotherapy session to start of breastfeeding to allow drug clearance from breast milk. If chemotherapy is restarted, breastfeeding must cease. Women taking tamoxifen should not breastfeed. Some researchers believe that breastfeeding after breast cancer will have a protective effect on the contralateral breast.
Another very common question is the probability of subsequent pregnancy after breast cancer treatment. Amenorrhea is a common problem following adjuvant chemotherapy given to premenopausal women with breast cancer. Chemotherapy can be detrimental to ovarian competence, devastating a woman's future fertility potential by damaging oocytes. The extent of damage is dependent on medication, drug dosage, and patient age.
For women at significant risk of future infertility, several strategies have been explored for fertility preservation including: Embryo and oocyte cryopreservation, Gonadotropin releasing- hormone (GnRH) agonist for ovarian protection and ovarian cortex cryopreservation.

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The question that might mind both the oncologist and the obstetrician more than the patient is the influence of subsequent pregnancy on recurrence and distant metastasis and on survival as general. Estrogens play a well known role in breast carcinogenesis and are dramatically increased during pregnancy. However, recent reports from the literature are reassuring.
Patients are generally advised to wait at least two years after diagnosis before becoming pregnant, because of the higher rate of recurrence of breast cancer in the first years after the diagnosis.