Once the pathologist has pathologically staged the breast cancer, they will further test the specimen for expression of estrogen and progesterone receptors. If the specimen expresses estrogen receptors, this patient will be a candidate for endocrine therapy. There are many ways to treat breast cancer endocrinologically, such as surgical removal of the ovaries (surgical debulking), pharmacological debulking, estrogen receptor antagonists (modulators), and aromatase inhibitors. However, estrogen receptor antagonist-tamoxifen is the most widely and longest used drug in clinical practice, which significantly reduces the recurrence rate of estrogen receptor positive breast cancer patients.
Side effects of tamoxifen usually include weight gain, burning sensation, and fatigue. Very rare side effects include thrombosis, endometrial tumors, and cardiovascular events. But the most important thing is that the chance of breast cancer recurrence is much greater than the chance of serious side effects of tamoxifen. The decision to apply tamoxifen treatment should be made by a joint discussion between the patient and the doctor. Aromatase inhibitors (anastrozole, letrozole, exemestane, etc.) are more effective than tamoxifen when applied to postmenopausal breast cancer patients.
Efficacy of tamoxifen: What is the duration of observation of the efficacy of tamoxifen? What are the options for endocrine therapy after tamoxifen? I have been taking tamoxifen for 18 months and have had good results in the first 15 months of review.
The time to observe the efficacy of tamoxifen is usually about one year. So 15 months is a good observation period for efficacy, to be sure. It seems that your current treatment is working well, so you should maintain the current basic treatment principles. Endocrine therapy drugs that can be considered if certain conditions are found later and the current treatment is not considered satisfactory are fulvestrant, exemestane and anastrozole.
Effectiveness of tamoxifen in metastatic breast cancer: How do I know that the anti-cancer drug is effective? For example, I am taking tamoxifen for metastatic breast cancer, how do I know if it is working?
For most anti-cancer drugs, the best way to know if it is working is to determine if the tumor is shrinking. This can be determined by imaging methods such as CT, MRI, PET-CT, isotope bone scans, and ultrasound. Some tumors can be detected by testing for tumor markers in the blood to know the effectiveness of treatment, such as CA125 for ovarian cancer and CA27.29 levels for certain breast cancers. Some cancers can be directly seen or touched, such as skin cancer and subcutaneous tissue tumors, so the changes of tumors can be understood through clinical examination.
Another method is to observe the efficacy of drugs through long follow-up. The length of time varies depending on the drug. Endocrine therapy, such as tamoxifen, may take several months to see if it is working. Some patients may even experience transient tumor enlargement in the first 1-2 weeks of endocrine therapy. Endocrine therapy can cause bone pain and skin damage, which can be considered as a sign of ineffective endocrine therapy. Therefore, the observation of the efficacy of endocrine therapy requires some patience. Chemotherapy can be considered if you wish to see the efficacy as soon as possible, but chemotherapy often has more obvious side effects.
Concept of hormone receptors: My cancer is hormone receptor positive, what is this concept?
The hormone receptor is a protein that is present on most breast cancer cells. The presence of this protein means that estrogen is needed for breast cancer growth. Breast cancers that contain estrogen receptors are generally slower growing and less likely to metastasize than cancers that do not contain estrogen receptors. Most importantly, in estrogen receptor-positive breast cancers, tamoxifen acts on the receptor to prevent metastasis and recurrence of breast cancer.
Tamoxifen and hysterectomy: I was diagnosed with ductal carcinoma in situ and postoperative pathology revealed microinfiltration. After axillary lymph node dissection (all lymph nodes were negative) I received 25 radiation treatments and tamoxifen. The latter caused severe uterine bleeding followed by hysterectomy and oophorectomy. Is tamoxifen still relevant to my treatment since there is no ovarian production of estrogen?
Tamoxifen does not require the ovaries to produce estrogen in order to work against breast cancer. Because the ovaries are not the only ones that produce estrogen in the body, other tissues also produce estrogen, so tamoxifen is equally effective in breast cancer patients with hysterectomized ovaries.
Tamoxifen and vaginal estrogen: I am taking tamoxifen for breast cancer, but I also have atrophic vaginitis and my doctor has recommended estrogen vaginal suppositories.
The effect of estrogen suppositories on the effects of tamoxifen is not known. However, considering that tamoxifen still has a good anticancer effect in premenopausal breast cancer patients who produce normal physiological amounts of estrogen, the use of estrogen suppositories will have little effect on the efficacy of tamoxifen. If patients do need it, we recommend the application of estrogen vaginal suppositories.
Relationship between tamoxifen and weight gain: Medical research data show that tamoxifen is not significantly associated with weight gain, but there are some data that say that weight gain of 10-25 kg was observed after taking tamoxifen, how can this be explained?
The only way to prove whether tamoxifen causes weight gain is a randomized controlled study. A study called the Breast Cancer Prevention Study (also known as the P-1 Study) enrolled 13,000 women, randomized to the tamoxifen group and the no-tamoxifen group, and concluded that there was no significant weight gain in the tamoxifen group compared to the control group. Any other data cannot be rejected to include the information obtained from the 13,000 women enrolled in the study.
Tamoxifen and ductal carcinoma in situ: I was diagnosed with highly differentiated, acne-necrotic ductal carcinoma in situ and underwent a modified radical mastectomy with no invasive carcinoma found in the pathology specimen and all 13 axillary lymph nodes were negative. Estrogen receptors were not tested. Is tamoxifen being recommended as further treatment? Does it make sense especially for protection of the contralateral breast? Is tamoxifen only effective in estrogen receptor positive patients?
In your individual case, tamoxifen can be beneficial because it reduces your risk of breast cancer in the contralateral breast. Your affected breast has already undergone complete surgical treatment, so there is no benefit of tamoxifen for the affected side. Although testing for hormone receptors in ductal carcinoma in situ is not required in some treatment guidelines, we advocate that receptor assays also be performed for ductal carcinoma in situ. Patients with estrogen receptor-positive breast cancer benefit significantly more from tamoxifen than receptor-negative patients. Whether a treatment is used is determined primarily by comparing its possible benefits with its possible side effects and is discussed by both the patient and the physician.
The therapeutic value of tamoxifen in estrogen receptor-negative breast cancer: My mother has undergone surgery, chemotherapy and radiotherapy for breast cancer and it is currently difficult to mobilize her for long-term oral tamoxifen therapy. The axillary lymph nodes are 1/16 positive with no distant metastases. Is tamoxifen effective when the estrogen receptor is weakly positive (ER+)? Are there any trials that have examined the effects of hormone-responsive drugs in estrogen receptor-negative breast cancer?
Breast cancers are routinely tested for their sensitivity to estrogen and progestin. The results are reported as ER+/PR+, ER+/PR-, ER-/PR+, ER-/PR- (ER estrogen receptor, PR progesterone receptor). Results are not only positive and negative, but can also include the percentage of hormone receptor-positive cells, which is called “weakly positive” if the ratio is low. The benefits of tamoxifen treatment for breast cancer patients are threefold: improved survival; reduced recurrence rates; and prevention of new breast cancers in the contralateral breast. These benefits have been observed in breast cancer patients who are ER+ and/or PR+ (even if weakly positive), but not in ER-/PR- patients. Therefore, the current recommendation is that patients with ER+ or PR+ breast cancer take tamoxifen or an aromatase inhibitor (anastrozole, letrozole, exemestane) for 5 years.
Patients with ER- breast cancer are first considered for chemotherapy based on their risk of breast cancer recurrence (breast cancer stage, pathological staging and histological grading). However, we noticed that in some prospective randomized studies, 5-10% of ER-negative breast cancer patients also benefited from endocrine therapy. There are two possible explanations for this phenomenon: one is that the receptor assay itself is in error leading to the appearance of a fraction of pseudo-estrogen receptor negativity (pseudo-ER-); the other may be that endocrine therapeutic agents act through other pathways of action, such as tamoxifen, which reduces the concentration of serum insulin-like growth factor-1, a strong stimulator of breast cancer cell proliferation.
Discontinuation of tamoxifen: After taking tamoxifen for 5 years for breast cancer, I was recently asked by my doctor to discontinue it and I gradually stopped taking it. However, two months after stopping the drug completely, I experienced a small amount of menstrual-like bleeding from my vagina. I am 66 years old and this naturally caused me to be alarmed. My doctor arranged a series of tests (blood tests, gynecological ultrasound, MRI, etc.) All tests were normal and my doctor recommended that I be examined by my OB/GYN. What are the symptoms of stopping tamoxifen?
The main symptoms of discontinuing tamoxifen include hot flashes, weight gain, and emotional instability. Most of them occur in women who are premenopausal at the time of breast cancer diagnosis or who are menopausal but receiving hormone replacement therapy. Hormonal disturbances in the body caused by discontinuation of tamoxifen may be responsible for uterine bleeding, and this phenomenon should be carefully examined.
Although the incidence is low, one of the most serious side effects of tamoxifen use is uterine cancer, which manifests itself as uterine bleeding. Therefore, an endometrial biopsy should be performed to rule out the possibility of uterine cancer.
Tamoxifen and endometrial cancer: Is tamoxifen related to endometrial cancer?
There is a correlation between tamoxifen use and increased risk of endometrial thickening, endometrial polyps, and endometrial cancer. The endometrial cancers found in the tamoxifen trials were found to be early and slow to develop, resulting in a higher cure rate. However, in recent years researchers have also found an increased incidence of some more aggressive endometrial malignancies (such as uterine sarcoma) in patients taking tamoxifen compared to those not taking the drug. This increased incidence of endometrial lesions has been shown even after discontinuation of the drug. This is why it is important for patients taking tamoxifen to have regular gynecological examinations. Despite these risks, experts agree that the benefits of tamoxifen in breast cancer patients outweigh the risks associated with its side effects.
Tamoxifen in patients with ductal carcinoma in situ: I am 52 years old (menopausal) and had a mastectomy. The pathology report was ductal carcinoma in situ combined with lobular carcinoma in situ, but no estrogen or progesterone receptors were detected. I underwent 6 weeks of radiation therapy. My doctor advised me to take tamoxifen for 5 years. My mother was paralyzed by a stroke at age 62. Is it appropriate for me to use tamoxifen when the receptor status is unknown?
Patients with ductal carcinoma in situ have been shown to benefit from tamoxifen in cases where the estrogen-progestin receptor status is unknown. Therefore, tamoxifen is routinely recommended for these patients. The risk of stroke from tamoxifen is negligible. As for your mother’s history of stroke paralysis is also not to be considered.
Tamoxifen treatment after tumor resection for estrogen receptor positive, smaller breast cancer: My wife underwent mastectomy for breast cancer (tumor diameter 0.8 cm) with negative sentinel lymph node biopsy. The pathology report was less than 10% positive for estrogen receptors. Is there a clear treatment pathway for this condition as there is for estrogen-progesterone receptor positive breast cancer?
Your wife’s breast cancer is in the early stage. The first and most important treatment is surgery, which has already been done. However, the risk of local recurrence after mastectomy is very high, so in principle postoperative radiotherapy should be administered.
Most of the extant data evaluating the benefit of chemotherapy for breast cancer target tumors larger than 1 cm. Although each patient’s situation is different and should be considered individually, most patients with smaller tumors will benefit relatively little from systemic chemotherapy. The decision to treat with chemotherapy depends on a comprehensive assessment of a breast cancer patient’s risk of recurrence, the benefits of chemotherapy, and side effects. In conclusion, for a patient with small, early-stage breast cancer, mastectomy combined with radiation therapy can be very effective, and the benefit of chemotherapy is less than its potential side effects. When deciding whether to treat with endocrine therapy, physicians should consider it along the same lines. If the breast cancer is estrogen and/or progesterone receptor positive, your doctor will recommend endocrine therapy because it is easy to treat, has few side effects, and offers reliable benefits. If the breast cancer is estrogen and progesterone receptor negative, as you describe, the benefit of tamoxifen is indeed lower.
There is no clear treatment pathway for smaller breast cancers that are estrogen receptor negative. Most patients with early stage breast cancer are very concerned about treating the disease completely when they are not using all of the current treatments (including surgery, chemotherapy, radiation therapy, endocrine therapy, etc.). As a patient this concern is understandable, but from the perspective of evidence-based medicine this concern is not necessary. In your wife’s case, what should be done after radiation therapy is close observation and follow-up, proper diet, smoking cessation and reduction of alcohol consumption. A scientific and healthy lifestyle is the best means to ward off all diseases.
What kind of drug is Anastrozole? My mother was diagnosed with breast cancer and has completed surgery, radiation treatment and the pathology report is negative for axillary lymph nodes. Anastrozole is currently recommended by her doctor. She suffers from rheumatoid arthritis and has severe pain. Will anastrozole treatment help relieve this pain?
Anastrozole is an endocrine therapy drug used for estrogen receptor positive, postmenopausal breast cancer patients. Endocrine therapy for estrogen receptor-positive breast cancer patients is as effective as chemotherapy but with fewer side effects. Endocrine therapy for breast cancer has developed rapidly in recent years. In particular, the emergence of aromatase inhibitors (anastrozole belongs to this group of drugs) and their clinical application have been widely documented to be more effective than tamoxifen in postmenopausal breast cancer patients. Anastrozole is used only in postmenopausal patients, which is determined by the mechanism of action of the drug and the physiological characteristics of women.
Although anastrozole is very effective as an endocrine therapy for breast cancer, we cannot give you any valuable opinion on its effect on rheumatoid arthritis.
Implications for endocrine therapy in patients with estrogen-progestin receptor weakly positive breast cancer: I am now 31 years old and have been diagnosed with breast cancer (estrogen-progestin receptor weakly positive). I have already completed breast cancer surgery and chemotherapy, is there any value in endocrine therapy for estrogen-progestin receptor weakly positive breast cancer patients?
Endocrine therapy is usually recommended for patients with weakly positive estrogen-progestin receptors. However, each patient should be treated individually according to his or her condition. Endocrine therapy drugs for breast cancer, such as tamoxifen, are easy to use, well tolerated and have few side effects, and their potential benefits outweigh their potential side effects. However, in principle this is a private decision and you should consider whether to apply endocrine therapy after discussing it with your doctor.