1. بنام خداوند جان وخرد

2. Breast cancer in pregnancy
دکتر زهرا مذهب
فوق تخصص خون و سرطان بالغین

4. Gestational Breast cancer or Pregnancy associated breast cancer
Is a breast cancer that is diagnosed during pregnancy, in the first postpartum year , or any time during lactation.

5. Pregnancy and breast cancer risk
Pregnancy is a time of breast development and hormone changes, so it affect breast cancer risk.
First pregnancy may increase the short term risk of breast cancer, it lowers the long term risk.
First child at age 35 or younger tend to get an overall protective benefit from pregnancy.
First child at later ages are at increased of breast cancer compared to the younger women.
Breast feeding lower the risk of breast cancer
Women having give birth only once at age 35 or older have a slightly higher risk compared to nulliparous women.

6. Incidence
Breast cancer is the most common cancer in pregnant and postpartum women
It occurs in about 1 in 3,000 pregnant women.
The average patient is between 32 to 38 years of age and because many women choose to delay childbearing, it is likely that the incidence of breast cancer during pregnancy will increase.
20%Br ca در سن كمتر از 30 و 5% در سن كمتر از 50

7. Pathology
Breast cancer pathology is similar in age-matched pregnant and non-pregnant women.
ER & PR positivity in pregnancy associated Br ca compared to non- pregnant approximately 25% versus 55-60%.
Hormone receptor assays are usually negative in pregnant breast cancer patients, but this may be the result of receptor binding by high serum estrogen levels associated with the pregnancy.
A study that used binding methods indicated similar receptor positivity between pregnant and non-pregnant women with breast cancer.
The study concluded that increased estrogen levels during pregnancy could result in a higher incidence of receptor positivity detected with immunohistochemistry than is detected by radiolabeled ligand binding, which is because of competitive inhibition by high levels of endogenous estrogen.

8. Diagnosis
The natural tenderness and engorgement of the breasts of pregnant and lactating women may hinder detection of discrete masses and early diagnoses of breast cancer.
Delays in diagnoses are common, with an average reported delay of 5 to 15 months from the onset of symptoms. Because of this delay, cancers are typically detected at a later stage than in a non-pregnant, age-matched population.
Even a one month delay in diagnosis can increase the risk of nodal involvement by 1 to 2 percent.

9. Detection of breast cancer
Pregnant and lactating women should practice self-examination and undergo a breast examination as part of the routine prenatal examination by a doctor. If an abnormality is found, diagnostic approaches such as:
Ultrasound and mammography may be used. With proper shielding, mammography poses little risk of radiation exposure to the fetus.
Since at least 25% of mammograms in pregnancy may be negative in the presence of cancer, a biopsy is essential for the diagnosis of any palpable mass (80% benign).
Diagnosis may be safely accomplished with a fine-needle aspiration, core biopsy, or excisional biopsy under local anesthesia.
To avoid a false-positive diagnosis as a result of misinterpretation of pregnancy-related changes, the pathologist should be advised that the patient is pregnant.
Mammograms should only be used, however, to evaluate dominant masses and to locate occult carcinomas in the presence of other suspicious physical findings.
Milk rejection sign

10. Stage Information for Breast Cancer Treatment and Pregnancy
Procedures used for determining the stage of breast cancer should be modified for pregnant women to avoid radiation exposure to the fetus.
If such scans are essential for evaluation, hydration and Foley catheter drainage of the bladder can be used to prevent retention of radioactivity.
Radiation exposure during the first trimester (>0.1 Gy) may lead to congenital malformations, mental retardation, and increased relative risk of carcinogenesis. Doses greater than 1 Gy may produce congenital abnormalities. Doses of 0.1 Gy may result in fewer defects.
Timing of the exposure to radiation relative to the gestational age of the fetus may be more critical than the actual dose of radiation delivered.

11. Chest x-rays should be used only when essential for making treatment decisions.A chest x-ray delivers Gy.
For the diagnosis of bone metastases, a bone scan is preferable to a skeletal series. A bone scan delivers Gy.
Evaluation of the liver can be performed with ultrasound, and brain metastases can be diagnosed with a magnetic resonance imaging (MRI) scan.
Data on MRI during pregnancy are not yet available, but gadolinium crosses the placenta and is associated with fetal abnormalities in rats.

12. Sentinel lymph node biopsy
Sentinel lymph node biopsy (SLNB) for staging of the regional lymph nodes can be performed safely during pregnancy.
It is advisable to inject colloid in the morning to reduce the time and dose of radiation.
Blue dye should not be used during pregnancy.
some experts recommend that SLNB only be used later in pregnancy.

13. Lactation Suppression of lactation does not improve prognosis.
If surgery is planned, however, lactation should be suppressed to decrease the size and vascularity of the breasts.
If chemotherapy is to be given, lactation should also be suppressed.

14. Management of breast cancer in pregnancy
Maternal treatment should adhere as closely as possible to standardised protocols for patients without concomitant pregnancy.
It is important that treatment is not delayed unless the delivery is already planned within the next 2–4 .
When BCP is diagnosed in the first trimester, each woman should have the option to terminate pregnancy, after careful counseling and information about all aspects.

15. Treatment early Stage Breast Cancer (Stage I and II)
Surgery is recommended as the primary treatment of breast cancer in pregnant women.
Modified radical mastectomy is the treatment of choice.
Conservative surgery with postpartum radiation therapy has been used for breast preservation.
Since radiation in therapeutic doses may expose the fetus to potentially harmful scatter radiation

16. If adjuvant chemotherapy is necessary, it should not be given during the first trimester to avoid the risk of teratogenicity.
Chemotherapy given after the first trimester is generally not associated with a high risk of fetal malformation but may be associated with premature labor and fetal wastage.
Studies using adjuvant hormonal therapy alone or in combination with chemotherapy for breast cancer in pregnant women are also limited.
Radiation therapy, if indicated, should be withheld until after delivery since it may be harmful to the fetus at any stage of development.

17. Late Stage Breast Cancer (Stage III and IV)
First-trimester radiation therapy should be avoided.
Chemotherapy may be given after the first trimester as discussed earlier.
Because the mother may have a limited life span, and there is a risk of fetal damage with treatment during the first trimester, issues regarding continuation of the pregnancy should be discussed with the patient and her family.
Therapeutic abortion does not improve prognosis.
(most studies show a 5-year survival rate of 10% in pregnant patients with stage III and IV disease)

18. Chemotherapy
cancer needs adjuvant chemo, it’s usually delayed until at least the second trimester.
If a woman is already in her third trimester when the cancer is found, the chemo may be delayed until after birth.
The birth may be induced (brought on) a few weeks early in some cases.
Chemo should not be given after 35 weeks of pregnancy or within 3 weeks of delivery because it can lower the mother’s blood counts. This could cause bleeding and increase the chances of infection during birth

19. chemotherapy
Chemotherapy during organogenesis (2–8 weeks) is associated with miscarriage, fetal death and major malformations.
After organogenesis, several organs including the eyes, genitals, hematopoietic system and the central nervous system remain vulnerable to chemotherapy.
Therefore, it is recommended to wait until 14 weeks of gestation before initiating cytotoxic treatment.
During the second and third trimester, chemotherapy can be administered relatively safely.

20. Hormone therapy
Hormone therapy is often used as adjuvant treatment after surgery or as treatment for advanced breast cancer in women with hormone receptor positive breast cancer.
Drugs used for hormone therapy of early breast cancer include tamoxifen, anastrozole, letrozole, and exemestane.
Hormone therapy should not be used during pregnancy because it can affect the fetus. It should be delayed until after the woman has given birth.

21. Targeted therapy
Trastuzumab is used as a part of adjuvant treatment after surgery, pertuzumab can be used with trastuzumab before surgery, and all of these drugs can be useful in treating advanced cancer.
But based on animal studies and reports of women who were treated during pregnancy, none of these drugs are considered safe for the fetus if taken during pregnancy.
Everolimus(Afinitor) and bevacizumab (Avastin) are also targeted drugs that can be used to treat advanced breast cancer. Again, neither of these drugs is safe to use during pregnancy.

22. Breastfeeding during cancer treatment
Most doctors recommend that women who have just had babies and are about to be treated for breast cancer should stop (or not start) breastfeeding.
If surgery is planned, stopping breastfeeding will help reduce blood flow to the breasts and make them smaller. This can help with the operation. It also helps reduce the risk of infection in the breast and can help avoid having breast milk collect in biopsy or surgery areas.
Many chemo, hormone, and targeted therapy drugs can enter breast milk and be passed on to the baby. Breastfeeding isn’t recommended if the mother is getting chemo, hormone, or targeted therapy.

23. Survival
Overall survival of pregnant women with breast cancer may be worse than in non-pregnant women at all stages; however, this may be primarily the result of delayed diagnoses.
Termination of pregnancy has not been shown to have any beneficial effect on breast cancer outcome and is not usually considered as a therapeutic option.

24. Referrence
1- Amant Fre´de´ric a, *,s, Deckers Sarah b , Van Calsteren Kristel, et. al; Breast cancer in pregnancy: Recommendations of an international consensus meeting , EUROPEAN JOURNAL OF CANCER xxx (2010)
2-Breast Cancer During Pregnancy; American cancer sosciety, 2014.

26. Survival rates after breast cancer during pregnancy
Pregnancy can make it harder to find, diagnose, and treat breast cancer. Most studies have found that the outcomes among pregnant and non-pregnant women with breast cancer are about the same for cancers found at the same stage, but not all studies agree. A 2013 study looked at more than 300 women diagnosed during pregnancy. During the 5-year follow-up, researchers reported comparable survival in women at the same stage whose breast cancer was found when they weren’t pregnant. Disease-free survival tended to be slightly shorter in the pregnant women.
Some doctors believe that ending the pregnancy may help slow the course of more advanced breast cancers, and they may recommend that for some women with advanced breast cancer. It’s hard to do research in this area, and good, unbiased studies don’t exist. Ending the pregnancy makes treatment simpler, but older studies that looked at pregnant women have reportedly not found that ending the pregnancy improves a woman’s overall survival or cancer outcome. Of note, there were some flaws that could have biased the outcomes of these studies. For example, the women who had more advanced disease were more likely to end their pregnancies. More recent studies on this can’t be found in the available medical literature, and it’s hard to know if outcomes would be different with more modern treatments.
Studies have not shown that the treatment delays, sometimes needed during pregnancy, have an effect on breast cancer outcome either. But this, too, has proven to be a difficult area to study. Finally, there are no reports showing that breast cancer itself can harm the baby.

27. Previous studies suggest a worse prognosis for postpartum breast cancer (PPBC) diagnosed within the first 12 months following delivery. We investigated this hypothesis in our setting through a retrospective pilot study.
RESULTS:
53 PPBC cases were matched with 103 controls. All PPBC patients were diagnosed with an invasive ductal carcinoma. Axillary lymph nodes were involved in 56.6% of cases and 13% were primary metastasized at diagnosis. A third was triple-negative and another third was HER-2-positive.The 5-year overall survival was 60% and 84% respec-tively for PPBC cases and control group. 5-year disease free survival was respectively 53% and 68%.
CONCLUSIONS:
We confirm that postpartum breast cancer behaves more aggressively than the matched non-PABC group. Longer follow-up and extension of the study group are necessary to confirm these findings.

28. Based on emerging preclinical and epidemiologic data, we propose that pregnant and postpartum cases be researched as distinct subsets of PABC to clarify the risk imparted by pregnancy and the events subsequent to pregnancy, such as breast involution, on breast cancer. Further, we highlight the importance of postpartum breast cancer as an area for further research to reduce the increased metastatic potential and mortality of PABC.
CONCLUSION:
Our results show that PABC is independently associated with poor survival particularly those diagnosed shortly post-partum. This underscores a possible impact of the pregnant breast microenvironment on the biology and consequently the prognosis of these tumors.
Copyright © 2012 Elsevier Ltd. All rights reserved.