Breast Cancer Anticancer Treatment and Shingles

Author: Akihiko Ozaki

Department of Breast Cancer Surgery, Jyoban Hospital, Iwaki, Fukushima

Editor: Yudai Kaneda

School of Medicine, Hokkaido University, Sapporo, Hokkaido

■Proposed administration of shingles vaccine.

Starting in late 2021, we propose administering the dry recombinant shingles vaccine Shingrix® (GlaxoSmithKline) to breast cancer patients who will receive anticancer agents over 50 years old because we often experience cases of shingles during anticancer treatment.

Shingles is a skin infection caused by the varicella-zoster virus. The trigger is said to be a weakening of the immune system due to aging, stress, or overwork. Naturally, the administration of anticancer drugs is a powerful trigger.

One million people in the United States are reported to develop shingles annually, and approximately 30% of people will develop shingles during their lifetime.

■ Breast cancer surgery forced to be postponed.

For example, a breast cancer patient in her 70s developed shingles after completing five months of preoperative anticancer drugs. Numerous blisters appeared on the inner side of the left lower extremity, which was typical of herpes zoster.

It was also when peripheral neuropathy, a side effect of the paclitaxel, was strongly affecting her lower limbs. She had a high degree of pain combined with numbness and could not walk.

On the other hand, since 72 hours had already passed since the onset of the disease at my examination, and there was no tendency toward deterioration, antiviral medication was not prescribed.

However, the scheduled breast cancer surgery had to be postponed. This is because it is recommended that the surgery be avoided immediately after the onset of shingles. It has been suggested that it may cause further immune depression and serious complications.

■Surgery should be avoided for about a month after the onset of shingles.

No actual data could be found on the length of time that surgery should be avoided after the onset of symptoms. However, based on the standards of other institutions, it is generally recommended that surgery should be avoided for about one month after the onset of symptoms.

Following this criterion, the surgery was postponed for a little less than a month from the scheduled date in this case. Fortunately, there were no complications or postherpetic neuralgia associated with the surgery, and no recurrence of the disease was observed until about 18 months after the surgery.

Postherpetic neuralgia is pain that persists for 90 days after the onset of herpes zoster. The cause is thought to be secondary nerve damage due to an inflammatory reaction caused by viral replication in the nerves. It is reported in approximately 20% of herpes zoster patients and is more likely to occur in elderly patients.

In addition to this patient, we have experienced several other cases of shingles development during anticancer drug implementation, all of which required interruption of anticancer drug treatment. Such interruption of anticancer drug treatment can harm the long-term treatment of the disease and should be avoided as much as possible. Based on the above experiences, we decided to introduce the dry recombinant shingles vaccine to our department.

■ Effectiveness of vaccine against shingles.

A Phase 3 clinical trial of dry recombinant shingles vaccine in healthy adults in 2003 and 2004, led by GlaxoSmithKline, was reported in the New England Journal of Medicine.

The former trial evaluated the vaccine's efficacy in patients over 50 years of age, while the latter was specifically limited to patients over 70 years of age.

To summarize the results, for healthy adults aged 50 years and older, the vaccine was 97.2% effective against shingles, and 91.3% effective only for those aged 70 years and older. For healthy adults 70 years of age and older, the vaccine was also reported to prevent 88.8% of postherpetic neuralgia. Furthermore, the incidence of side effects in the placebo and vaccine groups was reported to be comparable.

Additionally, Phase 2 and 3 clinical trials evaluating the vaccine's efficacy and safety in patients with solid tumors were reported in Cancer in 2019. Approximately half of the participants were breast cancer patients, and the results were highly suggestive.

Although this study was not able to evaluate the actual preventive effect of shingles in patients with solid tumors due to sampling size issues, it did report an increase in antibody titers due to vaccination. Regarding safety, side effects were more common in the vaccination group than in the placebo group.

A careful reading of the paper also reveals some challenges in introducing vaccines into actual practice, one of which is the timing of vaccination.

■Cost is also an issue for the shingles vaccine.

This study reported that vaccination on the same day as the start of anticancer therapy resulted in a smaller increase in antibody levels than vaccination eight days prior to the therapy (it is unclear how this affects the efficacy of prophylaxis). However, there are many cases where treatment is rushed, such as in patients undergoing preoperative chemotherapy. Therefore, it may not be possible to obtain informed consent for implementing anticancer drugs and vaccines and start treatment within a week.

In addition, we currently have limited experience in using dry recombinant shingles vaccine at Jyoban Hospital, and we have to order the vaccine on a case-by-case basis whenever there is a patient who wishes to be vaccinated. Therefore, the vaccine cannot be administered on the same day that informed consent is secured, and the patient is asked to revisit the hospital just for the vaccination. Of course, there is a possibility that as our experience in this area accumulates, hospitals will be able to stock even small quantities in the future.

Anyway, it is nonsense to delay treatment to increase antibody levels. Therefore, the best thing we can do is vaccinate as early as possible.

The cost can also be an issue. The dry recombinant shingles vaccine is expensive, costing 23,000 yen per dose, and it must be injected twice. No insurance will cover the cost. We feel guilty about asking patients to bear additional costs over the expensive breast cancer treatment they are already undergoing.

Because of these circumstances, we inform patients of the existence of the vaccine only as a "suggestion," and leave the actual decision of whether or not to take the vaccine to the individual patient. At present, my impression is that about two-thirds of the patients want to be vaccinated.

Many breast cancer patients are concerned that they may experience severe side effects or feel sick when anticancer drugs are administered. I want to continue to provide as much information as possible to relieve their anxiety as much as possible.