Pregnancy is safe for women with estrogen receptor positive breast cancer
David Cohen, M.D.·Published 21 March 2012·8 min read
Key points
New research has shown for the first time that it is safe for women who have been diagnosed with oestrogen receptor positive breast cancer to become pregnant, despite doctors' previous fears that pregnancy could boost levels of oestrogen in the body and cause the cancer to return.
Researchers have shown how estrogen receptor-positive breast cancer tumors become resistant to tamoxifen, the only approved hormonal therapy for premenopausal patients with this type of breast cancer.
Furthermore, patients who become pregnant appear to survive longer than those who do not.
Breast cancer is the most common cancer for women during their childbearing years.
New research has shown for the first time that it is safe for women who have been diagnosed with oestrogen receptor positive breast cancer to become pregnant, despite doctors' previous fears that pregnancy could boost levels of oestrogen in the body and cause the cancer to return.
In fact, the findings, to be presented today (Wednesday) at the eighth European Breast Cancer Conference (EBCC-8) in Vienna, suggest that becoming pregnant at any time following a diagnosis of breast cancer does not increase the risk of recurrence, even if the pregnancy occurs during the first two years after the diagnosis. Furthermore, patients who become pregnant appear to survive longer than those who do not.
Breast cancer is the most common cancer for women during their childbearing years. As women delay starting a family until they are older and the survival from breast cancer has improved, increasing numbers of breast cancer survivors want to have babies after their cancer treatment has finished. In a previous study, Dr Hatem A. Azim, Jr had shown that, despite fears that hormonal changes caused by pregnancy could prompt the cancer to return or become more aggressive, it appeared to be safe for these women to conceive. However, the study was unable to show whether this was the case for women with oestrogen receptor positive (ER+) disease – potentially the sub-group most likely to be affected by an increase in the hormone caused by pregnancy. In addition, other questions remained unanswered, including the therapeutic role of inducing abortion in these patients, timing of pregnancy and the safety of breastfeeding.
Therefore, Dr Azim, a medical oncologist at the Jules Bordet Institute (Brussels, Belgium), and colleagues carried out a study in several countries [1] in which they enrolled 333 [2] women who had become pregnant at any time following a breast cancer diagnosis and matched them with 874 similar breast cancer patients who did not become pregnant. Importantly, the study included only women whose oestrogen receptor status (positive or negative) and disease outcome were known. In addition, women in the control group had not relapsed at the time the matched case became pregnant; this enabled the researchers to adjust as far as possible for the "healthy mother effect" – a phenomenon whereby the results could be influenced by the fact the women who became pregnant might be healthier than breast cancer patients in the control group.
The researchers followed the women up for an average of 4.7 years after pregnancy. During this period, 30% of the total of 1,207 women had a recurrence of their disease.
Breast cancers that are estrogen-receptor-positive (ER-positive) are those that have estrogen receptors present on many of the cancer cells. Estrogen receptors are protein molecules that bind to the hormone, estrogen. ER-positive cancers rely on a source of estrogen to encourage proliferation (increase the number) of cancer cells. About 60% of all breast cancers are ER-positive.
Written and revised by
David Cohen, M.D.
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Because of their dependency on estrogen, most ER-positive cancers respond well to anti-estrogen therapies, such as Tamoxifen. The anti-estrogen therapies work by blocking the cancer cells’ estrogen receptors, effectively cutting off their nourishment. Finding out that your breast cancer cells do have estrogen receptors can be useful in determining an effective course of treatment.
Dr Azim said: "Out of all the women, 57% had ER+ disease, but the study showed there was no difference in the length of time women with either ER+ or ER negative [ER-] disease survived without their disease recurring compared with those who did not become pregnant. In addition, we found that patients who became pregnant within two years of breast cancer diagnosis appeared to have a better disease-free survival compared to those who did not become pregnant. However, a clear trend over time was not demonstrated; hence this finding should be interpreted with caution as it could be confounded by potential selection bias, and hence pregnancy within two years of diagnosis should be regarded as safe, and not as protective.
Researchers show how ER-positive breast cancer tumors become resistant to tamoxifen
Researchers have shown how estrogen receptor-positive breast cancer tumors become resistant to tamoxifen, the only approved hormonal therapy for premenopausal patients with this type of breast cancer. They also found that introducing a novel histone deacetylase inhibitor in hormone therapy treatment can overcome resistance to hormonal therapy.
"We always thought that resistance was primarily an inborn or genetic effect," said Pamela N. Munster, M.D., director of the Early-Phase Clinical Trials Program at the University of California, San Francisco. "But this is not the case. Tumors have found a way to modify their genes to become resistant. This process is called 'epigenetics,' where genes are turned on and off, but the sequence of DNA is not altered. We have also found that with this kind of breast cancer, we can prevent that resistance with histone deacetylase (HDAC) inhibitors."
Munster presented the findings at the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, held Nov. 12-16, 2011.
She and her colleagues found that estrogen receptor (ER)-positive breast cancer tumors alter their genes to create more AKT, a protein that spurs actions within the cell to keep it alive - the opposite of what tamoxifen is designed to do.
In a preclinical study, researchers introduced the HDAC inhibitor PCI-24781 at an early phase of tamoxifen treatment and found that it reverses the tumor's survival strategy of increasing production of AKT, thus stopping the tumor cells from developing resistance and leading to higher levels of cell death.
"A secondary objective in this study was to determine the impact of pregnancy on overall survival. We found that breast cancer patients who became pregnant also had a lower risk of death compared to their matched controls, irrespective of ER status."
Neither breastfeeding nor abortion (either in the form of a spontaneous miscarriage or an induced abortion) had an effect on the women's outcome. "Frequently when women with history of breast cancer become pregnant, some physicians advise them to have an abortion for fear that completing the pregnancy could have a detrimental effect on the outcome of their disease. We found that this was not true and the outcome was similar, irrespective of whether the pregnancy was completed or not. This was also the case both for women with ER+ and ER- disease. Hence, abortion should not be promoted for therapeutic reasons in these patients. The same analysis was done for breastfeeding, although we knew about breast feeding in only 30% of the patients, which hinders providing a firm conclusion in this regard," said Dr Azim.
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He concluded: "This is the first study to investigate the safety of pregnancy in breast cancer patients with ER+ disease, and which also adjusted for the 'healthy mother effect'. It shows convincingly that pregnancy any time following breast cancer diagnosis is safe, irrespective of ER status. This study provides strong evidence to help proper counselling of women seeking to become pregnant following completion of breast cancer therapy. However, this study does not address the optimal duration of adjuvant hormonal therapy in these women."
Score Predicts Late Recurrence in ER-Positive Breast Cancer – A new gene-based biomarker assay may help to estimate prognosis and make decisions about extended endocrine therapy in women with estrogen receptor–positive early breast cancer, new data suggest.
Researchers tested the biomarker, the Breast Cancer Index (BCI), among 249 women with estrogen receptor–positive early breast cancer from the MA.17 trial, in which women received 5 years of adjuvant tamoxifen therapy and, if still disease free, were then randomized to an additional 5 years of either letrozole (Femara) or placebo.
Study results, reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology, showed that with each 5-unit increase in the 10-unit BCI score, women’s odds of late recurrence nearly tripled.
The index as a whole was not helpful in predicting the benefit of added letrozole therapy in reducing recurrence risk. But one of its components, called H/I, was helpful: Women having a high H/I were about half as likely to have a recurrence if they received letrozole instead of placebo.
The study included any woman diagnosed with breast cancer before 2007 who matched the criteria for inclusion in the study. The patients had an average age of 34, ranging between 21-48 years old, with an equal proportion of patients receiving post-operative chemotherapy and hormonal therapy in both groups. Patients who did not become pregnant had to be free of cancer for an interval that was as long as the time that elapsed between a breast cancer diagnosis and the date of conception in the women who did become pregnant. The pregnant women were all in remission before conceiving.
Professor David Cameron, from the University of Edinburgh (Edinburgh, UK), and chair of EBCC-8 said: "This is an important study, as it can give women much more confidence that a wanted pregnancy after treatment for breast cancer does not necessarily mean a poorer chance of being able to live to bring up children. However, it is important to acknowledge that there are limitations in this kind of case control study, and so whilst an important piece of research, it cannot yet be taken as definitive proof that there is no adverse effect of a subsequent pregnancy. What it does suggest is that at worst any negative impact is small, and that it is likely that there is no detrimental effect of a subsequent pregnancy."
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Abstract no: 21, Wednesday 15.45 hrs, "Why does age matter?" session, Hall F2.
[1] The institutions and organisations that contributed patients to the study were: Danish Breast Cancer Cooperative Group (Denmark), European Institute of Oncology (Milan, Italy), Jules Bordet Institute (Brussels, Belgium), Vall D'Hebron University Hospital (Barcelona, Spain), University of La Paz (Madrid, Spain), Macerata Hospital (Macerata, Italy), and the International Breast Cancer Study Group. [2] The figures in this release are different to those in the abstract as they have been updated since the abstract was submitted. [3] The study was funded by grants from the European School of Oncology and Les Amis de l'Institut Bordet.
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