Managing Adverse Events for Women Receiving Adjuvant Breast Cancer Treatment

Clinical Course

A 46-year-old pre-menopausal woman was diagnosed with a IIIA (T2N2a) multicentric and multifocal intermediate-grade invasive lobular carcinoma of the right breast after presenting with a mass on screening mammogram. Biomarker testing on the initial biopsy revealed the tumor to be ER+ (Allred score of 8), PR+ (Allred score of 8), and HER2- (0 on immunohistochemistry). She underwent germline genetic testing, and there were no mutations or variants noted.

She proceeded to definitive surgery with a simple mastectomy with sentinel lymph node biopsy and prophylactic contralateral mastectomy. Pathology revealed a 3.1-cm invasive lobular carcinoma. Margins were negative. Four sentinel lymph nodes revealed metastatic carcinoma. She received 4 cycles of adjuvant doxorubicin and cyclophosphamide followed by 12 weeks of paclitaxel. At the completion of chemotherapy, she had amenorrhea. She went on to receive adjuvant ovarian suppression with goserelin and letrozole. At cycle 2, she was also started on abemaciclib 150 mg twice daily. For local control of her disease, she underwent adjuvant radiation to her mastectomy.

The patient developed hot flashes while receiving chemotherapy. Options for treatment were discussed. Venlafaxine XR 37.5 mg daily for 1 week was initiated, and the dose was increased to 75 mg daily. Her hot flashes improved. However, after 1 month, she reported that the hot flashes were still a concern and that she did not like the effects of venlafaxine on her mood. She requested to taper off the venlafaxine.

Next, oxybutynin 5 mg daily was initiated. She reported some relief, so it was continued for the next 4 weeks. Ultimately, it too was discontinued because of ongoing hot flashes in the context of amenorrhea throughout chemotherapy.

At the completion of adjuvant chemotherapy, the patient began ovarian suppression. At that point, her hot flashes became unbearable, and elinzanetant was added. Gabapentin was not used because she did not note a concern of painful neuropathy. In addition, she was also concerned about the side effects of gabapentin in the context of her post-chemotherapy fatigue.

The patient reported vaginal dryness and was counseled on the use of non-hormonal moisturizers and lubricants, such as Revaree and coconut oil. Those options have continued to be helpful.

Adjuvant abemaciclib was initiated at 150 mg twice daily. The patient experienced grade 1 diarrhea and is taking 2 mg of loperamide daily to help control it.

Discussion

This patient’s experience of amenorrhea is consistent with that of many premenopausal women who receive adjuvant doxorubicin for breast cancer. Chemotherapy regimens containing either doxorubicin or cyclophosphamide can be associated with a higher likelihood of prolonged amenorrhea. The duration and intensity of chemotherapy further increase the likelihood of treatment-related amenorrhea.

Hot flashes are a common occurrence in women with amenorrhea and loss of ovarian function. The incidence is reported at 3 out of 4 women in perimenopause. Therefore, oncology clinicians routinely address these concerns with breast cancer survivors. Low-dose systemic estrogen is contraindicated in HR+ cancers, but the safety of intravaginal estrogen is not known. Many patients do their own research and often come into the clinic looking for advice on products such as evening primrose oil, black cohosh, and Estroven, etc. These types of products are not well studied, but some studies indicate they can interfere with the metabolism or efficacy of selective estrogen receptor modulators and aromatase inhibitors.¹

Non-hormonal options can be effective but offer a host of side effects, and each option must be tailored to the unique health concerns of each patient. The options for patients with breast cancer are similar to those of patients undergoing perimenopause who do not have a history of breast cancer. According to the Menopause Society, the options for treatment include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), oxybutynin, gabapentin, fezolinetant, and elinzanetant.²

SSRIs such as citalopram and escitalopram have been found to be effective. Alternatively, SNRIs including venlafaxine and desvenlafaxine have a similar benefit for hot flashes, although no head-to-head trials have been conducted. These two classes can be beneficial in treating depression, anxiety, and hot flashes. Patients on tamoxifen should not take paroxetine because of the metabolism concerns with CYP2D6.³ It is important to note that these medications must be tapered when discontinued in order to lessen withdrawal symptoms. The patient in this case study had improvement of her hot flashes but noticed a negative change in her mood. She was subsequently tapered off of the venlafaxine XR. Oxybutynin, an anticholinergic agent, was prescribed to the patient, but it too was minimally effective and ultimately discontinued.

Neurokinin 3 receptor (NK3R) antagonists fezolinetant and elinzanetant are newer options for managing hot flashes. Studies have demonstrated improvement in the severity of hot flashes and sleep disturbances with these medications.⁴ The major side effect is elevation of liver enzymes in a small percentage of patients. Liver enzyme monitoring is recommended during the first year of treatment. Thus far, the patient in this case has found better control of her hot flashes on elinzanetant without any side effects.

Gabapentin has been shown to be effective in managing hot flashes in women. Often patients find it makes them sleepy or fatigued. It is an excellent choice for patients who have trouble sleeping related to their hot flashes. Furthermore, it can help with neuropathic pain. Many patients with breast cancer receive taxane chemotherapy, which can cause neuropathy. Choosing this drug can help with both concerns. A slow increase in this medication to a therapeutic dose can offer improved tolerance of the drug and overall effectiveness of gabapentin for these adverse events.

Another consideration for patients with breast cancer who are on adjuvant endocrine therapy is vaginal dryness. Initial management should include non-hormonal moisturizers and lubricants. Routine use of moisturizers (2-3 times per week) can be effective. These include products such as Replens, K-Y Liquibeads, HYALO GYN, and Revaree. In a study by Carter et al., 101 postmenopausal women used a non-hormonal hyaluronic acid vaginal gel for 12 weeks, with results indicating improvement of symptoms in up to 92% of the patients in this cohort.⁵

In addition, lubricants should be used with sexual activity to minimize discomfort. Lubricants can be water based, silicone based, or oil based. Oil-based lubricants such as coconut oil can be effective, but they can degrade condoms. If vaginal dryness and atrophy contribute to a decrease in the patients’ quality of life despite these measures, patients and their care team can discuss the safety of vaginal estrogen. Studies are limited and present safety concerns in regard to recurrence. In the patient in this case study, non-hormonal options have been offered. She has an advanced-stage HR+ disease, so avoiding vaginal estrogen is important.

Arthralgias are a common adverse event from adjuvant aromatase inhibitors. Arthralgias can range from mild joint stiffness to life-altering joint pain. Many women struggle to complete the full course of treatment. Drug holidays and switching to an alternate aromatase inhibitor can be helpful. Fortunately, the patient in this case has not experienced joint or bone pain.

The CDK4/6 inhibitor abemaciclib has reported side effects including myelosuppression, stomatitis, nausea, hair loss, rash, and pneumonitis. There is up to a 90% incidence of diarrhea.⁶ Patients can control it with anti-diarrheals or even bulk-forming agents such as psyllium fiber. This has been effective for the patient in this case study.

The AP’s Role

The AP should assess toxicity at each clinic visit to help guide the appropriate treatment. APs can also encourage lifestyle change such as diet, exercise, and smoking cessation. Hormonal changes can lead to weight and mood concerns. Some of the options for treatment for hot flashes can also address mood, pain, or neuropathy problems. Often women don’t report vaginal dryness and assume their sexual dysfunction is an expected side effect without options for improvement. Therefore, it is important APs to broach this topic during visits.

Breast cancer surgery may also lead to altered body image. This, too, may weigh into a patient’s sexual concerns. APs may have more time to spend with the patient, allowing for proper identification of all of the patient’s concerns.

Conclusion

Life after a diagnosis of breast cancer can be very different for patients. The patient in this case study has bothersome hot flashes, vaginal dryness, and diarrhea on adjuvant treatment. APs can help navigate these concerns while finding a good fit for a better quality of life.

References

1. Cleveland Clinic. Symptoms. Cleveland Clinic website. Accessed August 24, 2026. https://my.clevelandclinic.org/health/symptoms
2. Shufelt CL, Brown V, Carpenter JS, et al. The 2023 nonhormone therapy position statement of The North American Menopause Society Menopause. 2023;30(6):573-590. doi:10.1097/GME.0000000000002200.
3. Cronin-Fenton DP, Damkier P, Lash TL. Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol. 2014;10(1):107-22. doi:10.2217/fon.13.168.
4. Pinkerton JV, Simon JA, Joffe H, et al. Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials. JAMA. 2024;332(16):1343-54. doi:10.1001/jama.2024.14618. 
5. Carter J, Baser RE, Goldfrank DJ, et al. A single-arm, prospective trial investigating the effectiveness of a non-hormonal vaginal moisturizer containing hyaluronic acid in postmenopausal cancer survivors. Support Care Cancer. 2021;29(1):311-22. doi:10.1007/s00520-020-05472-3.
6. Verzenio (Abemaciclib). Lilly website. Accessed August 24, 2026. verzenio.lilly.com