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Breast cancer

Breast Cancer

Epidemiology:

Breast cancer is widely recognized as one of the most prevalent cancers affecting women globally, with an estimated 0.3 million new cases reported in the United States alone in 2023 1. Despite significant advancements in treatment modalities, spontaneous remission (SR) in breast cancer remains an exceedingly rare phenomenon; documented instances of SR typically constitute less than 5% of total breast cancer cases 2. Epidemiological evidence suggests that various biological and environmental factors may contribute to the cessation of tumor growth or regression, although the mechanisms behind SR are not well understood 3. As SR events are often only distinguished in cases of dramatic and sustained tumor reduction, the true prevalence of these occurrences likely goes underreported, complicating efforts to fully comprehend the potential for spontaneous regression within the patient population 4.

Clinical Characteristics:

To date, there have been over 35 reported cases of SR of either primary or metastatic breast carcinoma. Several clinical patterns emerge from the documented cases. The age at the time of regression ranges from 31 to 86 years, with a peak incidence between 50 and 70 years. All reported cases involve females, consistent with the gender distribution of breast cancer. Remission has been observed in both primary breast tumors and metastatic sites, most frequently within the breast itself, though instances have also been documented in the axillary lymph nodes, pleura, bone, skin, and lungs. See Table 1 below for detailed case information.

Histological Characteristics:

Patients who experienced spontaneous remission of breast carcinoma typically presented with palpable breast masses or radiologic abnormalities consistent with malignancy, and the diagnosis was confirmed through histopathological examination of biopsy or surgical specimens demonstrating invasive carcinoma. Most cases involved localized disease confined to the breast, although remission was also observed in regional or distant sites, including the axillary lymph nodes, pleura, bone, lungs, and skin. Remission was verified by follow-up imaging or histological assessment showing complete disappearance or marked reduction of malignant cells. Nearly all SR cases were associated with durable clinical stability or long-term remission, far exceeding the expected course of untreated breast cancer.

Proposed Contributing Mechanisms:

Multiple mechanisms have been proposed to explain spontaneous remission in breast carcinoma. The most frequently reported involve immune activation triggered by biopsy-induced trauma, which may stimulate local or systemic antitumor immune responses leading to tumor remission. Other hypothesized contributors include hormonal influences such as menopause-related changes, infection-induced immune stimulation, ischemic or vascular events, and immune-mediated cytotoxic responses. Historical cases also referenced factors like erysipelas infection, arsenic exposure, or dietary and hygienic interventions, whereas more recent reports emphasize immune mechanisms involving tumor-infiltrating lymphocytes and immunogenic cell death. Collectively, these observations suggest that spontaneous regression in breast carcinoma likely results from a complex interplay of immunologic, vascular, and hormonal pathways.

Site and Extent of Remission:

The breast was the primary site in all reported cases of spontaneous remission of breast carcinoma, with remission most frequently observed in the primary tumor itself rather than in metastatic sites. When metastases were involved, remission was most commonly noted in the axillary lymph nodes, followed by the pleura, bone, skin, and lungs. A few cases also documented remission at mastectomy or biopsy sites, often attributed to trauma-induced or immune-mediated mechanisms. In several modern reports, remission occurred following biopsy-induced immune activation, vascular thrombosis, or immune-mediated cytotoxic responses. The follow-up duration among these cases ranged from a few months to several decades, with many patients maintaining prolonged remission or clinical stability. Unlike most solid tumors, spontaneous remission in breast carcinoma has occasionally been complete and durable, highlighting its distinctive immunobiological characteristics.

Table 1: Breast Cancer SR Cases and Clinical Characteristics

Author–year

Age/sex

Primary site

Remission site

Proposed mechanisms

Follow-up

Mohr, 18885

83/F

Breast

Breast

Erysipelas infection, Arsenic effect

Not reported

Gould, 18976

43/F

Breast

Breasts, Lung, Femur

Not reported

Not reported

Osler, 19017

31/F

Breast

Sternum, Right eye

Not reported

Not reported

Steward, 19258

81/F

Breast

Not reported

Dormant carcinoma cells

31 years

Bowlby, 19259

Not reported

Breast

Not reported

Not reported

24 years

Bulkley, 192510

45/F

Breast

Breast, Axillary glands

Dietary and hygienic measures

29 years

Bulkley, 192510

44/F

Breast

Breast, Axillary glands

Very active treatment

19 years

Bulkley, 192510

44/F

Breast

Breast

Very active measures

16 years

Bulkley, 192510

38/F

Breast

Breast, Axillary glands

Dietetic, hygienic, and medical treatment

9 years

Smithers, 195211

46/F

Breast

Breast

Menopause

16 months

Smithers, 195211

Not reported/F

Breast

Breast

Menopause, Homeopathy

Not reported

Smithers, 195211

64/F

Breast

Breast

Menopause related

Not reported

Dao, 196212

65/F

Breast

Lungs

Altered adrenal cortical activity

17 months

Bloom et al., 196213

Not reported/F

Breast

Not reported

Not reported

8 years 3 months

Lewison, 197614

Not reported/F

Breast

Not reported

Not reported

Not reported

Meares, 197615

49/F

Breast

Breasts, Spine

Intensive meditation

Not reported

Krutchik et al., 197816

60/F

Breast

Ribs, Pleura

Immunological factors

Not reported

Meares, 197717

49/F

Breast

Not reported

Intensive meditation

Not reported

Meares, 198118

54/F

Breast

Mastectomy scar

Intensive meditation

Not reported

Ross et al., 198219

60/F

Breast

Pleura, Bone

Not reported

72 months

Nauts, 198420

42/F

Breast

Breast

Toxin therapy

48 years

Bezic, 200821

43/F

Breast

Breast

Foreign body giant cell reaction

Not reported

Oya et al., 200922

71/F

Breast

Breast

Biopsy-induced trauma, immune response

Not reported

Takayama et al., 201923

67/F

Breast

Axillary lymph node

Immunological reactions

Not reported

Cserni et al., 201924

72/F

Breast

Breast, Axillary lymph nodes

Tumor-infiltrating lymphocytes

Not reported

Tomasini, 202025

86/F

Breast

Skin (cutaneous metastases)

Cytotoxic immune response

6 months

Ohara et al., 202126

59/F

Breast

Breast

Immunogenic cell death

Not reported

Sasamoto et al., 202327

52/F

Breast

Breast, Axillary lymph nodes

Biopsy-induced immune response

Not reported

Qureshi et al., 202328

84/F

Breast

Breast

Biopsy-induced immune response

Not reported

Yilmaz et al., 202429

65/F

Breast

Breast

Biopsy-induced trauma

Not reported

Yilmaz et al., 202429

65/F

Breast

Breast

Biopsy-induced trauma

Not reported

Kannari et al., 202530

81/F

Breast

Breast

Vascular thrombosis

Not reported

Spiegel et al., 198931

Nakagawa et al., 198132

Puah, 201133

64/F

Breast

Right femoral shaft

3 months

Matusuda et al., 201434

47/F

Right breast

Needle trauma, hormonal factors

Dussan, 200835

68/F

Right breast

None reported

Sadatomo, 201136

50/F

Breast

Lung metastases

Host immune system

Mackay, 190737

37/F

Breast

Clinical remission by December 28th, 1906

Mackay, 190737

37/F

Chest and axilla

Absorption of exudate

Hodenpyl, 191038

37/F

Breast

Breast

Immune response vs tumor growth substances

Hodenpyl, 191038

37/F

Neck, breast, abdominal, liver

Selective necrosis of carcinoma cells

D'Alessandris, 202339

76/F

Breast

Breast

Immune response

D'Alessandris, 202339

80/F

Breast

Breast

Excessive immune response

Kong, 202140

38/F

Breast

Femur

None reported

2 years

Lilienthal, 191341

58/F

Wound

Well for years

Boyd, 191442

48/F

Abdomen and lymph glands

Fluid accumulation cessation

Improvement noted after March 14, 1913

Gravitz, 198543

Misdiagnosis, spontaneous remission, immune system

Cured for 14 years

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