International Medical News

No.516ISSN 0535-1405

INTERNATIONAL MEDICAL NEWSInternational Medical Society of Japan
Since 1925
March 30, 2023
Published by International Medical Society of Japan,Chairman,Board of Directors:Kenichi Ishibashi, MD, PhD
Editors: K. Ito, MD, PhD, T. Kondo, MD, PhD,K. Ichihashi, MD, PhD, T.Murakami, PhD,R.Nagai, MD, PhD,I.Taniguchi, MD, PhD,andT.Yamazaki,MD,PhD

1-11-9-3F Kamiuma,Setagaya-ku,
Tokyo154-0011,Japan.
TEL03(5486)0601 FAX03(5486)0599 E-mail:imsj@imsj.or.jp https://www.imsj.or.jp/

The 457th International Symposium on TherapyThe 457th International Symposium on Therapy was held by the Zoom Webinar onJanuary 19, 2023. Dr. Koichi Ito, Director of the International Medical Society of Japan(IMSJ), presided over the meeting.

Breast cancer frontline
Introductory Message from the Chair
Koichi Ito, MD, PhD
Director, IMSJ【Discourse】
Discourse:
Rev.Hiroaki Miyoshi
Chief Priest
Hongakuzan Myojuji
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LectureⅠ
Latest trends in breast imaging diagnosis: Personalized screening and role of MRIguided biopsy
Mitsuhiro Tozaki MD, PhD
Director of Department of Radiology
Sagara Hospital
In Japan, the mortality rate of breast cancer has not decreased, despite mammographybased breast cancer screening having become more widely available. Therefore, thesignificance of the mammography-based screening has been discussed, and it is now
considered necessary to conduct the screening according to the risk of each individual(personalized screening) rather than uniformly applying the same screening procedure
for all women in Japan.
In 2016, the results of a randomized controlled trial (J-START) conducted to
examine the usefulness of mammographic screening with and without breast
ultrasonography in women in their 40s were published in Lancet. The results showed thatof the screening methods, (1) 18% (34/184) of breast cancers were detected bymammography alone, and (2) 33% (61/184) of breast cancers were detected by breast
ultrasonography alone. In conclusion, mammography alone is not sufficient for breast
cancer screening in Japanese women in their 40s. It is an urgent necessary to discuss theindications for adding breast ultrasonography to mammographic screening for early
detection of breast cancer.
In 2022, the European Society of Breast Imaging (EUSOBI) reported the following:“EUSOBI recommends such supplemental MRI screening to be offered to women withextremely dense breasts, from age 50 to 70, and at least every 4 years, preferably every
2 to 3 years. MRI can be used as a stand-alone screening technique （ withoutmammography）”. The background for this recommendation is based on the findings ofa study conducted in 40373 women with extremely dense breasts in 2019. In this study,
16.5 individuals out of 1000 were found to have breast cancer. On the other hand, theresults of the J-START study showed that the number of individuals detected by screening
to have breast cancer is about 3.2 out of 1000 (117/36752) for mammography and 5.0
out of 1000 (184/36752) for mammography combined with breast ultrasonography.
Although there was an increase by about 1.5 times, the fact has become clear that thenumber of individuals detected is expected to increase only by 2 out of 1000. Therefore,

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we wonder if it might actually be useful to introduce ultrasonography for breast screening
in Japan in the future.
In Europe and the United States also, breast ultrasonography is not widely
accepted as a screening tool, and MRI is recommended for women at high risk. The
lifetime risk of 20% or more of developing breast cancer (lifetime risk) is defined as “highrisk”. Tools such as the Tyrer-Cuzick model and Gail model are used to evaluate thelifetime risk of breast cancer. In Japan, due to the absence of such assessment tools, it isdifficult to immediately adopt the concept of “high risk” cases as in Europe and the U.S.
The first step in screening of high-risk women should be MRI screening for hereditary breastand ovarian cancer (HBOC) syndrome. We conducted the research entitled “A study ofthe usefulness of MRI screening in patients with BRCA1/2 pathogenic variants” since 2014.
The results showed that the frequency of breast cancer detected by MRI was 9% (2/22).
This is the first prospective study in Japan to confirm the usefulness of MRI screening forhigh-risk women.
MRI screening is used in combination with MRI-guided biopsy for high-risk women.
MRI-guided biopsy has been used in Europe and the U.S since 1994. However, in Japan,
it began to be covered by the National Health Insurance system only in April 2018, about
11 years after the first MRI-guided biopsy was performed in 2007. According to our data
since 2007, the rate of malignancy detected by MRI-guided biopsy is 38% (115/301). Thus,
MRI-guided biopsy is considered to be an essential procedure not only in the Western
population, but also in the Japanese population.
In April 2020, risk-reducing surgery and breast MRI surveillance began to becovered by the National Health Insurance system for patients with a history of HBOC. Asa result, the number of institutions undertaking MRI-guided biopsy has graduallyincreased, but the examination is still performed at only 13 institutions. Considering theincreasing number of individuals that would be expected to undergo MRI screening in
the future, it is important to immediately increase the number of institutions that would
make MRI-guided biopsy available.

LectureⅡ
Recent Strategies for Breast Cancer Therapy~from diagnosis to treatment~
Fumi Saito MD,PhD
Department of Breast and Endocrine Surgery,12

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Toho University Medical Center Omori Hospital
Considering the incidence of malignant diseases, breast ranks first among Japanese
females, with the number of affected patients growing, especially among females aged
≥40 years. However, breast cancer has the fifth highest mortality rate among malignant
diseases, indicating a low mortality rate despite frequency. This can be attributed toimprovements in diagnostic techniques, including breast cancer screening, and novel
drug therapeutics. Moreover, the extensive role of mammary gland surgery needs to beconsidered. We report the latest strategies in diagnosis, surgical treatment, perioperative
drug therapy, and post-recurrence treatment.
・Breast cancer diagnosis
Breast cancer is a malignant disease with a relatively good prognosis. However,maintaining the quality of life in survivors post-treatment may be challenging. In young
breast cancer patients, hereditary breast cancer and fertility-preservation should beconsidered post-diagnosis. Hereditary breast cancer accounts for approximately 10% ofbreast cancers, with certain syndromes attributed to multiple genetic abnormalities.
Among them, BRCA1/2 gene mutation-induced hereditary breast cancer and ovariancancer syndrome (HBOC) has a high frequency. From 2020, BRCA1/2 genetic testing will
be covered under insurance for patients diagnosed with breast cancer ˂45 years of age.
In patients diagnosed with HBOC preoperatively, contralateral mastectomy, to prevent
contralateral breast cancer development, and salpingo-oophorectomy, to prevent
ovarian cancer, can be performed simultaneously during breast cancer surgery.
Perioperative drug therapy for breast cancer includes anticancer drug therapy,
molecular target drug therapy, and endocrine therapy, with continuous endocrine
therapy recommended for ≥5 years. Secondary amenorrhea (infertility) due toanticancer drugs and endocrine therapy needs to be addressed in breast cancer
survivors who desire to have children. Therefore, fertility-preservation surgery is widely
recommended

beforeinitiating

drug

therapy.

Currently,

cryopreservation

offertilized/unfertilized eggs or ovarian tissue is recommended in Japan. However, no clear
consensus has been established regarding the risk of aging in pregnancy and subtypes
due to prolonged standard treatment.
・Surgical treatment
To date, breast-conserving surgery has been the main surgical procedure employed inbreast cancer surgery. However, since breast reconstruction surgery has been coveredby health insurance since 2013, there has been a growing tendency to perform
simultaneous breast reconstruction post-mastectomy. Breast reconstructive techniques
include those that utilize artificial materials and those using autologous tissue. Considering

13International Medical Newsthe timing of surgery, primary reconstruction is simultaneously performed with breast
cancer surgery, whereas secondary reconstruction is performed after a certain period
post-surgery. Selecting the most suitable surgical method is essential, considering factors
such as the patient's condition, desires, and body type.
・Perioperative drug therapy
Previously, the purpose of neoadjuvant chemotherapy (NAC) for advanced breast
cancer was tumor shrinkage and breast tissue preservation. In 2022, revised guidelines
included a 'residual disease-guided approach' after NAC for breast conservation. Breast
cancer is broadly classified into four subtypes, with drugs and therapeutic effects
markedly differing considering each subtype. Patients who achieve a good therapeuticeffect with NAC tend to have a good prognosis. Conversely, postoperative drugs distinct
from those that afforded a complete response need to be selected for patients whofailed to achieve a complete response. The potential of molecular-targeted drugs andimmune-check inhibitors for NAC has been explored, dramatically improving therapeuticeffects.
Anticancer drugs, molecular-targeted drugs, and endocrine therapy are selected basedon each subtype and risk for postoperative drug therapy. Considering endocrine therapy,
continued treatment for 5 years was previously recommended; however, extending
therapy for 7 to 10 years has been recommended depending on the risk. The latest
guidelines recommend combining cyclin-dependent kinase 4 and 6 inhibitors andanticancer agents, for example, combined with endocrine therapy to treat recurrence.
Drug therapy is becoming progressively individualized.
・Treatment after recurrence
Post-breast cancer surgery, recurrence and metastasis are often observed in the bone,
liver, and lung. Surgical resection of recurrent lesions remains the first choice, despite poor
evidence suggesting an improved prognosis. Drug therapy for each subtype differs, andsubtypes occasionally differ between primary and metastatic lesions. Therefore,
confirming the subtype by repeat biopsy of the metastatic lesion is recommended before
initiating treatment for recurrence. Since 2019, gene panel testing has been covered byhealth insurance. Treatment options are expected to extend to patients who wouldexperience anyrecurrence after completing recommended treatments.
Currently, more individualized treatment is recommended, from breast cancer diagnosis
to treatment for recurrence.

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