Chemotherapy

1946 · Treatment · Foundations

Nitrogen mustard: first chemotherapy for lymphoma, reported 1946

In August 1942 doctors at Yale gave a patient with lymphoma an injectable drug related to mustard gas. His tumours shrank, then returned, and he died that December. Wartime secrecy shrouded the work, and the first medical reports appeared in 1946, describing the drug for Hodgkin disease, lymphoma and leukemia.

Patient JD, with lymphosarcoma refractory to radiotherapy and surgery, received intravenous nitrogen mustard at Yale from 27 August 1942: 0.1 mg/kg, 10 daily injections. Biopsy afterwards showed no tumour; counts then fell, tumours recurred by day 49, and he died on 1 December 1942 (day 96); autopsy showed marrow aplasia. First reports followed in 1946 (Science; JAMA). Single-patient chart review, no comparison group.

1946 · Treatment · Thyroid cancer

Radioiodine therapy of functioning thyroid cancer metastases

In the 1940s a physician at Montefiore Hospital in New York, Samuel Seidlin, gave radioactive iodine to people whose thyroid cancer had spread. A 1999 memoir dates the first such patient to 1943 and says some tumours took up the iodine only after the normal thyroid was removed. His group's report appeared in JAMA in 1946.

Historical series; the 1946 JAMA report (Seidlin, Marinelli, Oshry) has no PubMed abstract and was not read, so no outcome figures are recorded. Per a 1999 memoir (Siegel): first patient 1943, previously thyroidectomised with functioning metastases of thyroid adenocarcinoma; Seidlin held that removing normal thyroid raises TSH and removes competition for iodine, inducing metastases to function; patients followed 1942 to 1955. Hertz and Roberts treated hyperthyroidism (31 March 1941).

1948 · Treatment · Childhood acute lymphoblastic leukemia (ALL)

Aminopterin produces temporary remissions in childhood leukemia

In 1948 Sidney Farber and colleagues reported that aminopterin, a drug that blocks folic acid, brought temporary remissions to some children with acute leukemia. The remissions were short and the drug caused serious side effects, but a 2013 review describes the report as opening the era of chemotherapy for the disease.

Uncontrolled clinical series of children with acute leukemia given the folic acid antagonist aminopterin (N Engl J Med, 3 June 1948). A later account (Spain and Kadan-Lottick 2012) reports 16 critically ill children treated: 10 had remissions that were temporary, 2 had none and 4 died within a few months; the paper documents 5 of the 10. Toxicity included stomatitis with mouth ulceration, internal hemorrhage and marrow aplasia. Counts come from the later account, not the paywalled 1948 text.

1948 · Treatment · Foundations

Aminopterin produces temporary remissions in childhood leukemia

In 1948 Sidney Farber and colleagues reported that aminopterin, a drug that blocks folic acid, brought temporary remissions to some children with acute leukemia. The remissions were short and the drug was toxic, but the report showed that a chemical could drive leukemia back, and methotrexate, a close relative, is still used today.

Uncontrolled clinical series of children with acute leukemia given the folic acid antagonist aminopterin (NEJM, 3 June 1948). Later accounts (Spain and Kadan-Lottick 2012; Izraeli 2022) describe 16 children studied, 10 with remissions that were temporary, and five documented in detail in the paper; main toxicity severe stomatitis with oral ulceration. These counts come from the later accounts and were not checked against the full 1948 text.

1950 · Understanding · Foundations

Hospital case-control study links smoking to lung carcinoma (1950)

In 1950 Richard Doll and A. Bradford Hill compared the smoking habits of London hospital patients with and without lung cancer. Almost all the men with lung cancer had smoked, and heavier smokers were over-represented. The authors concluded that smoking is an important factor; later follow-up of British doctors strengthened the case.

Hospital case-control study in 20 London-region hospitals: 649 men and 60 women with carcinoma of the lung, compared with patients with other cancers and with non-cancer controls. Non-smokers were 0.3% of men and 31.7% of women with lung carcinoma versus 4.2% and 53.3% of controls. The authors concluded that smoking is an important factor. A 1951 to 2001 cohort of 34,439 male doctors followed (Doll 2004).

1950 · Treatment · Hodgkin lymphoma

Peters links stage to survival after radiotherapy (1950)

In 1950 Vera Peters in Toronto reported survival for 113 histologically proven cases of Hodgkin disease treated with radiotherapy, grouped by how far the disease had spread. Those with the least spread did best. A historian writes that her figures suggested cure might be possible; she did not claim it, and she later recalled that acceptance took about ten years.

Peters (Toronto, 1950), as described by Cowan 2008: 113 histologically proven cases treated with radiotherapy and grouped into three stages by extent of disease. Stage I: 5-year survival 88%, 10-year 79%, median survival over 11.6 years (stage II over 7.8 years, stage III 1.9 years). Per Cowan, Peters did not claim cure in this paper. Figures are from Cowan's account; the 1950 paper was not opened.

1951 · Understanding · Cervical cancer

HeLa cells: a cervical cancer line and the ethics questions it raised

A cell strain derived from a cervical cancer in February 1951 became known as HeLa and has been used in laboratories worldwide. Published accounts name the patient as Henrietta Lacks and describe tissue passed to a researcher without her knowledge or permission, as was common practice then. The case later fed debate about consent for research on tissue samples.

Scherer et al. (J Exp Med, 1953) report that strain HeLa had been maintained in vitro since its derivation in February 1951 from what they call an epidermoid carcinoma of the cervix; Lucey et al. (2009) describe the patient's disease as an aggressive adenocarcinoma. Schwarz et al. (1985) report HPV 18 DNA integrated in HeLa cells; Landry et al. (2013) describe high aneuploidy and some rearrangements indicative of chromothripsis in a HeLa Kyoto line.

1952 · Understanding · Foundations

TNM: Denoix's anatomic extent classification takes shape (1943-1954)

Working from a French cancer registry begun in 1943, the surgeon Pierre Denoix and colleagues developed one common scheme for recording how far each cancer had spread. It grew into the tumour, node and metastasis (TNM) system, which the international cancer union adopted and still publishes as a shared language for describing cancer extent.

Clinical classification of anatomic tumour extent developed by Pierre Denoix at the Institut Gustave Roussy, Paris. Registration began in 1943; a unified classification was proposed in 1947; a 1952 report added a metastasis component; a 1954 article set out local, regional and distant extent. UICC first recommendations 1958, brochures from 1960, TNM pocket book 1968; first AJCC manual 1977.

1953 · Treatment · Childhood acute lymphoblastic leukemia (ALL)

Mercaptopurine and methotrexate: from 1953 to ALL maintenance

In 1953 doctors reported that mercaptopurine, a drug designed to interfere with purine metabolism, produced remissions in some children with acute leukemia, including some whose disease had stopped responding to a folic acid blocker. Mercaptopurine and methotrexate are now given together in the continuation phase of ALL treatment.

Burchenal et al. (Blood, November 1953), uncontrolled series: 6-mercaptopurine produced good clinical and hematologic remissions in 15 of 45 children with acute leukemia and partial remissions in 10 more; among 24 children with disease resistant to amethopterin (methotrexate), 5 had good and 5 partial remissions. Resistance to 6-MP appeared to develop somewhat faster than to folic acid antagonists. FDA's table dates mercaptopurine 11 September 1953 and methotrexate 7 December 1953 (original approvals in Drugs@FDA).

1953 · Treatment · Chronic myeloid leukemia

Busulfan (Myleran) reported in chronic myeloid leukaemia

On 31 January 1953 the Lancet published D. A. Galton's results of treating chronic myeloid leukaemia with busulfan (Myleran), alongside a paper on the drug's chemistry. A report from 1961 describes this as the first use of busulfan in the disease and as a challenge to radiotherapy, the standard until then.

Galton DA, Lancet, 31 January 1953: results of treatment with busulfan (Myleran) in chronic myeloid leukaemia, published with a companion paper by Haddow and Timmis. PubMed holds no abstract for either paper and the full texts were not read, so no patient numbers or response data are given. A 1961 Belfast series of 25 patients states that Galton was first to use busulphan in chronic granulocytic leukaemia.

1953 · Origin · Testicular germ cell tumors

Dixon and Moore's clinicopathological study of testicular tumours

In 1953 the journal Cancer published a clinicopathological study of testicular tumours by F. J. Dixon and R. A. Moore. A history of gonadal pathology calls it an important paper of the 1950s. This site has not read the paper itself, so it does not describe its findings or any classification it proposed.

Dixon FJ and Moore RA, Cancer 1953, "Testicular tumors; a clinicopathological study", reprinted in J Urol in 2002 (PubMed types the reprint as a seminal and historical article). Only bibliographic data were read: PubMed holds no abstract and the text was not opened, so case numbers, histological categories and outcomes are not reported. Young (2005) calls it an important 1950s paper and notes that the authors also wrote the first series fascicle on testicular tumours.

1955 · Treatment · Chronic lymphocytic leukaemia

Chlorambucil: the oral alkylating-agent reference for CLL

Chlorambucil is an oral chemotherapy tablet. A 1955 clinical report of the drug in lymphoma is cited here by title only and may not cover CLL. In terms of survival, a 1999 pooled analysis of randomised trials in CLL supported no treatment for most early-stage patients and chlorambucil alone as first-line treatment for most advanced disease.

Chlorambucil (CB 1348) in malignant lymphoma: Galton 1955, title only. CLL Trialists' Collaborative Group meta-analysis (1999): 2048 early-stage patients, six trials, 10-year survival 44% immediate vs 47% deferred chemotherapy (difference -3%, 95% CI -10% to 4%); 2022 patients, ten trials, 5-year survival 48% with combination chemotherapy and with chlorambucil (difference 0%, 95% CI -6% to 5%). FDA original action on Leukeran: 18 March 1957.

1956 · Treatment · Foundations

Methotrexate reported active against choriocarcinoma (1956)

In 1956 Min Chiu Li, Roy Hertz and Donald Spencer reported methotrexate treatment of three patients with metastatic choriocarcinoma or a related tumour, all of whom improved. A later biography credits Hertz and Li with the first medical cure of a solid cancer. A 2011 review puts the cure rate for these tumours today above nine in ten.

Proc Soc Exp Biol Med 1956 (Li, Hertz, Spencer): three patients with progressive metastases (two choriocarcinoma, one chorioadenoma destruens) received repeated courses of methotrexate; gonadotropin fell towards normal and all improved clinically, with radiological regression of lung metastases; the authors called for more observations. Am J Obstet Gynecol 1961: five years' experience (no abstract). 2003 biography: first medical cure of a solid cancer. 2011 review: overall cure rate above 90%.

1957 · Origin · Acute myeloid leukaemia (including APL)

Early reports of acute promyelocytic leukemia, 1957 and 1959

Papers titled "Acute promyelocytic leukemia" appeared in Acta Medica Scandinavica in 1957 (Hillestad) and, in French, in the Schweizerische Medizinische Wochenschrift in 1959, where the title of Bernard and colleagues refers to a study of 20 cases. Only the titles are available, so what the papers reported, and who first described the disease, is not settled by these records.

Hillestad, Acta Med Scand 1957, "Acute promyelocytic leukemia" (PubMed: no abstract; content not read). Bernard and colleagues, Schweiz Med Wochenschr 1959 (French; the English form of the title is a study made on 20 cases; no abstract; content not read). No clinical details are recorded. Wang and Chen (2008) describe APL as having a severe bleeding tendency and a fatal course of only weeks.

1957 · Treatment · Colorectal cancer

Heidelberger 1957: fluorinated pyrimidines as tumour inhibitors

In 1957 Heidelberger and colleagues published a short paper in Nature titled 'Fluorinated pyrimidines, a new class of tumour-inhibitory compounds'. This record rests on the title only, because no abstract or text was read. Fluorouracil is now widely used in cancer treatment, and it is the backbone of the colon cancer adjuvant regimens later in this timeline.

Heidelberger C, Chaudhuri NK, Danneberg P et al., Nature 1957, 'Fluorinated pyrimidines, a new class of tumour-inhibitory compounds'. PubMed holds the title and bibliographic record only (no abstract) and the text was not read, so no experimental design or results are recorded. A 2003 review describes 5-fluorouracil as widely used in cancer treatment.

1960 · Understanding · Chronic myeloid leukemia

The Philadelphia chromosome: a consistent minute chromosome

In 1960 Peter Nowell and David Hungerford, working in Philadelphia, reported chromosome studies of leukemia cells. A 1961 paper found a similar shortened chromosome in nine of ten patients with chronic granulocytic (now myeloid) leukemia, and the authors called it a consistent change in a specific human cancer. It was later named the Philadelphia chromosome.

Pre-banding cytogenetics. JNCI 1960: in 2 chronic granulocytic leukemia cases an abnormality probably involving the Y chromosome. Science 1960 abstract (not opened): seven cases per Radich 2022; Nowell 2007 differs. JNCI 1961 abstract: 10 patients, similar abnormality in 9 (loss of about half the long arm of a small acrocentric chromosome). A 9;22 translocation was demonstrated in the 1970s (Nowell 2007).

1960 · Understanding · Foundations

A minute chromosome found in chronic myeloid leukemia (1960)

In 1960 Peter Nowell and David Hungerford noticed an unusually small chromosome in leukemia cells from patients with chronic myeloid leukemia. It was later named the Philadelphia chromosome, shown to come from an exchange of material between chromosomes 9 and 22, and became the target of the drug imatinib.

A characteristic small chromosome in leukemic cells, first reported in two chronic cases (JNCI, July 1960); a 1961 JNCI paper reports 10 patients, 9 with a similar abnormality. Accounts of the 1960 Science abstract and of the naming differ (Nowell 2007; Radich 2022). Rowley (Nature 1973): in nine consecutive patients, a 22q deletion with extra material on 9q, suggesting a 9;22 translocation. BCR-ABL is targeted by imatinib.

1961 · Treatment · Childhood acute lymphoblastic leukemia (ALL)

Combination antileukemic agents tested in children with ALL

In 1961 Emil Frei and colleagues reported a comparison of mercaptopurine and methotrexate, given in sequence or together, in acute leukemia. In children, remissions were more frequent with both drugs than with either alone, and the typical remission lasted 4 to 5 months with all three. A 1965 report found that adding methotrexate did not lengthen remission beyond mercaptopurine alone.

Frei 1961 (Blood; abstract), children with acute lymphocytic leukemia: remission rate 59% with mercaptopurine plus methotrexate, 47% with mercaptopurine, 29% with methotrexate; median duration of complete remission 4 to 5 months for all three; n and remission definition not in the abstract. Frei 1965 (Blood; abstract): combinations gave at least additive remission rates; alternating versus concurrent agents, and combination versus mercaptopurine alone, did not prolong remission; intrathecal folic acid antagonist did not either but reduced meningeal leukemia.

1962 · Treatment · Bladder cancer

Radical cystectomy series: Whitmore and Marshall 1962, Stein 2001

A 1962 journal report by Whitmore and Marshall carries the title 'Radical total cystectomy for cancer of the bladder: 230 consecutive cases five years later'; only the title is available to this site, so its results are not summarised. A later series of 1,054 patients reported that 68% were free of recurrence at five years.

Whitmore and Marshall (J Urol 1962): '230 consecutive cases five years later' of radical total cystectomy (title only; no outcome data recorded). Stein et al. (J Clin Oncol 2001): 1,054 patients, radical cystectomy with bilateral pelvic lymphadenectomy, median follow-up 10.2 years; recurrence-free survival 68% at 5 and 66% at 10 years; 27 perioperative deaths (2.5%); 246 patients (24%) node-positive, 5-year recurrence-free survival 35%.

1962 · Treatment · Hodgkin lymphoma

Kaplan: radical radiotherapy and the Stanford trials

In 1962 Henry Kaplan of Stanford published a paper on radical radiotherapy for Hodgkin disease that had not spread widely. That same year Stanford began a long series of randomised trials. Over twenty-two years they involved more than eight hundred people, and the authors reported steady improvement in remission and survival.

Kaplan 1962: title 'The radical radiotherapy of regionally localized Hodgkin's disease' (no abstract; text not read). Stanford randomised trials, initiated 1962 (Rosenberg and Kaplan 1985): 132 patients with clinical stage I, II and III disease enrolled on radiation trials from 1962 to 1967; more than 800 patients over 22 years; remission rate, duration and survival progressively improved across protocol eras. No arm comparisons extracted.

1962 · Treatment · Multiple myeloma

Melphalan, then melphalan plus prednisone, in myeloma

Melphalan was evaluated in myeloma in 1962. A 1969 report on 183 people treated with melphalan found that those given melphalan with prednisone responded more often than those given melphalan alone, and their median survival was about six months longer. A 1998 overview found no difference in deaths between combination chemotherapy and melphalan plus prednisone.

Alexanian 1969, publisher abstract: 183 patients treated with melphalan, objective response 43%; among evaluable patients 70% responded to melphalan plus prednisone, 35% to intermittent melphalan and 19% to daily melphalan; median survival with melphalan-prednisone was about six months longer than with melphalan alone. Bergsagel 1962: evaluation of L-phenylalanine mustard in myeloma (title only). Myeloma Trialists' overview (6,633 patients, 27 trials): response 60.0% versus 53.2% for combination chemotherapy versus MP; no mortality difference (P=0.6).

1963 · Treatment · Kidney cancer (renal cell carcinoma)

Robson and radical nephrectomy for renal cell carcinoma (1963, 1969)

Two papers on radical nephrectomy, an operation that removes the kidney, for kidney cancer were published in the Journal of Urology in 1963 and 1969, with C. J. Robson as first author. They are cited here by title only, so their methods and results are not summarised.

Robson CJ, J Urol 1963: 'Radical nephrectomy for renal cell carcinoma'; Robson CJ, Churchill BM, Anderson W, J Urol 1969: 'The results of radical nephrectomy for renal cell carcinoma'. Neither PubMed record has an abstract and the text was not available, so no technique, staging or outcome data are reported. PubMed indexes a 2002 reprint of the 1969 paper as a Seminal Article and Historical Article.

1964 · Understanding · Lung cancer

1964 US Advisory Committee report links cigarettes to lung cancer

In January 1964 the US Surgeon General released the report of a ten-member expert committee that weighed evidence from many studies. It judged cigarette smoking to be causally related to lung cancer in men, with data for women pointing the same way, and found the risk lowered by stopping.

Advisory Committee report released 11 January 1964. Using 29 retrospective studies of lung cancer, seven prospective studies and clinical, autopsy and experimental evidence, it judged cigarette smoking causally related to lung cancer in men. Average male cigarette smokers had approximately a 9- to 10-fold risk and heavy smokers at least 20-fold; risk rose with duration and daily number of cigarettes and was diminished by stopping. Data for women were less extensive but pointed the same way.

1966 · Treatment · Neuroblastoma and Wilms tumour

Actinomycin D and vincristine in Wilms tumour treatment, 1966-67

In 1966 Sidney Farber published a JAMA paper on chemotherapy in leukaemia and Wilms tumour, and in 1967 a JAMA paper reported vincristine in the management of Wilms tumour. A 2016 history says Farber's group added the antibiotic dactinomycin (actinomycin D) and reached an 80 per cent survival rate in 1966.

Farber (JAMA 1966) and Sullivan et al. (JAMA 1967, on vincristine replacing preoperative irradiation) are cited by title only; no results are taken from them. Nakayama 2016 (review abstract) gives survival of 32% with surgery alone (Ladd, 1940), 47% with surgery plus radiotherapy (Gross and Neuhauser, 1950) and 80% after dactinomycin was added (Farber, 1966). The FDA table dates dactinomycin for Wilms tumour 12-10-1964.

1966 · Understanding · Prostate cancer

Gleason grading (1966) and ISUP Grade Groups (2014)

In 1966 a pathologist, Dr Gleason, published a classification of prostate cancer by the growth patterns of its glands. A 2025 review describes five patterns, with the two most common in a tumour added into a score from 2 to 10. In 2014 pathology experts agreed updated pattern rules and five simpler Grade Groups, reported alongside the Gleason score.

Gleason's 1966 classification (no PubMed abstract) is described in a 2025 review as five growth patterns from the VACURG studies, with predominant and secondary patterns added to a score of 2 to 10. The 2014 ISUP consensus (65 pathology experts and 17 clinicians, 19 countries) assigned cribriform and glomeruloid glands to pattern 4 and, with 90% consensus, adopted Grade Groups 1 to 5, validated in over 20,000 prostatectomy specimens.

1967 · Treatment · Childhood acute lymphoblastic leukemia (ALL)

Asparaginase: from 1967 leukemia reports to a core ALL drug

In 1967 a JAMA report described remissions in human leukemia with L-asparaginase, an enzyme that breaks down the amino acid asparagine. It later became a component of ALL regimens, and a 2013 review describes a long-acting pegylated form as the first-line asparaginase in the United States.

Hill et al. (JAMA, 27 November 1967) reported remission in human leukemia with L-asparaginase (title only; no abstract). FDA: asparaginase (Elspar) January 1978; pegaspargase February 1994 (hypersensitivity to native forms) and 24 July 2006 (first-line, multi-agent ALL). DFCI 05-001 (Place 2015): 463 randomised; asparaginase-related toxicity 28% IV pegaspargase vs 26% IM native E coli (p=0.60); 5-year DFS 90% vs 89% (p=0.58).

1969 · Treatment · Foundations

Platinum compounds found to be antitumour agents: path to cisplatin

A 1965 experiment found that products from a platinum electrode stopped bacteria from dividing, and a 1969 paper reported platinum compounds as a new class of antitumour agents. Cisplatin reached the clinic in the 1970s; a 1977 series of patients with disseminated testicular cancer treated with cisplatin, vinblastine and bleomycin reported complete remission in nearly three of four.

1965 (Nature): platinum electrolysis products inhibited E. coli division. 1969 (Nature): platinum compounds inhibited mouse sarcoma 180 and leukaemia L1210. 1977 (Ann Intern Med): 50 patients with disseminated testicular cancer received cisplatin, vinblastine and bleomycin; 3 inevaluable; 74% complete and 26% partial remission; 85% disease-free after surgery for residual disease; 2 drug-related deaths; 38 alive, 32 disease-free at 6+ to 30+ months. Single-arm series.

1969 · Understanding · Melanoma

Clark levels and Breslow thickness: microstaging of melanoma

Two systems linked how deeply a melanoma had grown to a person's outlook. Clark graded invasion by the layers of the skin; Breslow related outcome to the tumour's measured thickness. Thickness remains the central measurement in modern melanoma staging, while the level of invasion has been dropped from the thin-melanoma criteria.

Clark (Cancer Res, indexed March 1969) is a title-only record; a 2014 review dates Clark's level-of-invasion system (levels I-V) to 1966 and Breslow's thickness observation (Ann Surg, November 1970) to 1970. Neither paper has a PubMed abstract; no case numbers or outcomes are stated here. AJCC 2009: mitotic rate replaced level of invasion for T1b. AJCC eighth edition: thickness to the nearest 0.1 mm; T1a under 0.8 mm without ulceration; T1b 0.8-1.0 mm.

1970 · Treatment · Foundations

MOPP combination chemotherapy for advanced Hodgkin disease (1970)

In 1970 DeVita, Serpick and Carbone reported combination chemotherapy for advanced Hodgkin disease, the four-drug regimen later called MOPP. Follow-up of patients treated at the US National Cancer Institute showed that most reached complete remission and about two in three of them stayed free of disease for over ten years, so advanced Hodgkin disease came to be seen as curable.

National Cancer Institute series of 198 patients with advanced Hodgkin disease treated with MOPP (mechlorethamine, vincristine, procarbazine, prednisone). 1980 analysis: 80% complete remission; 68% of complete responders disease-free beyond 10 years. 1986 update, median follow-up 14 years: of 188 patients with confirmed Hodgkin disease, 157 (84%) achieved complete response and 101 (66%) stayed disease-free beyond 10 years. Uncontrolled single-institution series.

1970 · Treatment · Hodgkin lymphoma

MOPP: combination chemotherapy for advanced Hodgkin disease

In 1970 researchers at the US National Cancer Institute reported a four-drug combination, later called MOPP, for advanced Hodgkin disease. Long-term follow-up showed that most people reached complete remission and about two in three of them stayed free of disease for over ten years. The authors concluded the disease appeared curable by chemotherapy.

Uncontrolled single-institution series of MOPP (mechlorethamine, vincristine, procarbazine, prednisone) in advanced Hodgkin disease; the 1970 report has no PubMed abstract. 1980 analysis of 198 patients: 80% complete remission, 68% of complete responders disease-free beyond 10 years. 1986 update, median follow-up 14 years: of 188 patients with confirmed Hodgkin disease, 157 (84%) achieved complete response and 101 (66%) stayed disease-free beyond 10 years.

1971 · Treatment · Breast cancer

Tamoxifen: from ICI 46474 to adjuvant standard

In 1971 a small Manchester study gave an anti-oestrogen tablet, later known as tamoxifen, to forty-six women with advanced breast cancer. About one in five clearly responded and side effects were mild. Later trials and pooled analyses showed that about five years of tamoxifen after surgery lowers recurrence and death in oestrogen-receptor-positive disease.

Single-arm study (Cole 1971): ICI46474 in 46 postmenopausal women with advanced disease; clear response in 10 (22%). NSABP B-14 (N=2644, node-negative, ER-positive): disease-free survival 83% vs 77% with tamoxifen vs placebo (P<0.00001). EBCTCG 2011 (ER-positive disease, n=10,645): recurrence RR 0.53 in years 0-4 and 0.68 in years 5-9; breast cancer mortality RR 0.71, 0.66 and 0.68 in successive 5-year periods.

1971 · Understanding · Breast cancer

The estrogen receptor and receptor-guided endocrine therapy

Elwood Jensen's laboratory work from the late 1950s led to the idea of an oestrogen receptor in target tissues. In 1971 he and colleagues reported on oestrogen receptors and breast cancer response to adrenal removal. Measuring the receptor in tumour tissue later became a way to predict who would benefit from hormone treatment.

Qualitative history milestone; no trial data. Jensen et al. (Natl Cancer Inst Monogr 1971) addressed estrogen receptors in relation to breast cancer response to adrenalectomy (title only; no abstract available). Jensen's receptor work dates from the late 1950s (O'Malley and Khan 2013). Reviews describe receptor measurement as a test predicting outcome of antihormonal therapy and as the target for developing tamoxifen.

1971 · Detection · Breast cancer

First screening RCTs: HIP (1971) and Swedish counties (1985)

Two early randomised trials invited women to mammography and compared deaths from breast cancer with women not invited. The New York HIP trial and a Swedish trial in two counties each reported fewer breast cancer deaths in the invited group. Both reports had limits, and later trials and analyses have debated how large the benefit is.

HIP (women aged 40-64; mammography plus clinical examination, four rounds): about 25% lower breast cancer mortality at 18 years in women aged 40-49 and 50-59 at entry, with the author questioning utility in the forties. Swedish county trial (162,981 enrolled; 134,867 aged 40-74 analysed): interim results to end of 1984 showed 31% lower breast cancer mortality and 25% fewer stage II or more advanced cancers in the invited group. The 1971 HIP paper has no abstract.

1971 · Treatment · Childhood acute lymphoblastic leukemia (ALL)

Total Therapy and CNS-directed prophylaxis at St Jude

St. Jude Children's Research Hospital began "total therapy" for childhood leukemia in 1962, adding treatment aimed at the central nervous system to combination chemotherapy. Early reports described fewer nervous-system relapses, and a 2013 review credits an early study with cures in about half of 35 patients.

St Jude single-institution series: cranial irradiation (2400 R) plus intrathecal methotrexate added early in remission to combination chemotherapy. Aur 1971 (Blood): of 35 consecutive children, 20 of 30 who attained remission and completed the initial phases were in continuous complete remission for 23 to 30 months; nervous system relapse ended remission in 3, hematological relapse in 5. Earlier regimens: CNS leukemia ended remission in over half the patients, median 11 months. Abstract-level; no randomised comparison described.

1971 · Understanding · Foundations

National Cancer Act of 1971 creates the National Cancer Program

On 23 December 1971 US President Richard Nixon signed the National Cancer Act. It gave the director of the National Cancer Institute wide powers to plan a national cancer programme and sent the institute's budget proposal straight to the President and Congress. Nixon described the effort as the 'war on cancer', language of that time.

Legislative milestone, not a clinical study. Public Law 92-218 (Senate Bill 1828), enacted 23 December 1971, created the National Cancer Program under the NCI director; established an 18-member National Cancer Advisory Board and a three-member President's Cancer Panel; sent the NCI budget proposal directly to the President; funded 15 new cancer research centres, local control programmes and an international cancer research data bank.

1971 · Understanding · Foundations

Two-hit hypothesis: retinoblastoma as a two-mutation cancer (1971)

In 1971 A. G. Knudson analysed 48 cases of retinoblastoma, a childhood eye cancer, and proposed that it arises after two mutational events. In the inherited form one is present from birth; in the non-inherited form both happen in the same cell. The model explained why some carriers have no tumour and others have tumours in both eyes.

Statistical model based on observations on 48 retinoblastoma cases and published reports. Hypothesis: retinoblastoma is caused by two mutational events; in the dominantly inherited form the first is germinal and the second somatic, in the nonhereditary form both are somatic. Poisson statistics with a mean of three tumours per carrier accounted for carriers without tumour, unilateral and bilateral disease and multiple tumours in one eye. Mutation rates were estimated as approximately equal.

1971 · Understanding · Hodgkin lymphoma

Ann Arbor staging classification for Hodgkin's disease

In 1971 a committee published a staging classification for Hodgkin's disease that grouped patients by how far the disease had spread. It let doctors choose treatment by stage and compare results between centres. Later meetings added scans and bulk, and its terminology is still used in today's lymphoma staging.

The 1971 report of the Committee on Hodgkin's Disease Staging Classification (Carbone et al) is cited by Munir et al (2023) as the origin of the Ann Arbor classification, a mainly anatomical system. The Cotswolds meeting (Lister 1989) kept the structure and added CT, an X suffix for bulk over 10 cm and a CR(u) response category. The Lugano classification (Cheson 2014) modified Ann Arbor terminology, kept A or B only for Hodgkin lymphoma and added PET-CT for FDG-avid disease.

1972 · Understanding · Testicular germ cell tumors

Skakkebaek reports possible carcinoma in situ of the testis

In 1972 N. E. Skakkebaek published a two-page article in The Lancet titled 'Possible carcinoma-in-situ of the testis'. A later review credits him with first characterising a non-invasive precursor of testicular germ-cell tumours, now called germ cell neoplasia in situ. The article itself was not read for this site.

Skakkebaek NE, Lancet 1972: a single-author, two-page article (title only in PubMed; text not read). Later sources describe the lesion: Karellas and Damjanov (2007) credit Skakkebaek with first characterising the non-invasive precursor; Dieckmann and Skakkebaek (1999) report carcinoma in situ next to germ-cell tumour in about 90% of cases, with a 50% probability of progression within 5 years if untreated.

1973 · Understanding · Chronic myeloid leukemia

Rowley: banding suggests a 9;22 translocation in CML (1973)

In 1973 Janet Rowley studied cells from nine consecutive people with chronic myelogenous leukemia using new chromosome staining methods. The Philadelphia chromosome in all nine was a shortened chromosome 22, and extra material appeared at the end of one chromosome 9 in all cells. She suggested that material had been exchanged between the two chromosomes, a translocation.

Nature 1973 letter (publisher abstract): 9 consecutive CML patients, quinacrine fluorescence and Giemsa banding. Ph1 was a 22q- deletion in all 9; all cells carried added material on the long arm of one chromosome 9 (9q+), about equal to that missing from 22q-. The author suggested a previously undetected 22q;9q translocation. Later accounts describe a demonstrated reciprocal t(9;22) (Radich 2022; Minciacchi 2021).

1975 · Understanding · Chronic lymphocytic leukaemia

Rai staging: lymphocytosis plus anatomy predicts survival

In 1975 Rai and colleagues proposed sorting CLL into five stages using blood counts and a physical examination: lymphocytes alone, then swollen glands, an enlarged spleen or liver, low red cells, and low platelets. In their 125 patients, median survival ranged from over 12 years at the earliest stage to under 2 years at the last two.

Rai et al., Blood 1975, proposed clinical staging of CLL as progressive accumulation of lymphocytes: stage 0 lymphocytosis only; I with enlarged nodes; II spleen or liver; III anaemia; IV thrombocytopenia. In 125 patients, median survival from diagnosis (months) was above 150 (stage 0), 101, 71, 19 and 19 (stage IV); 71 for the series. Stage remained prognostic after adjustment for age and sex.

1975 · Understanding · Endometrial cancer

Two 1975 studies link estrogen use to endometrial cancer

In 1975 two studies in the New England Journal of Medicine reported that women with endometrial cancer had used estrogen medicines far more often than comparison women. In 1996 a randomised trial found that estrogen alone raised rates of endometrial overgrowth, while adding a progestin kept rates close to placebo.

Case-control studies (N Engl J Med, 4 Dec 1975): Smith, 317 cases vs 317 controls, risk 4.5 times greater with estrogen; Ziel, 94 cases, risk-ratio estimate 7.6, rising from 5.6 to 13.9 with duration. Mack 1976: risk ratio 8.0 (95% CI 3.5-18.1) for any estrogen. PEPI (randomised, 596 women, 3 years): simple hyperplasia 27.7% with estrogen alone vs 0.8% with placebo; estrogen-plus-progestin regimens similar to placebo (P = .16).

1975 · Understanding · Foundations

Hybridoma technique makes monoclonal antibodies possible (1975)

In 1975 Georges Köhler and César Milstein fused antibody-producing cells with tumour cells to create cell lines that make identical antibodies of a chosen specificity in unlimited amounts. The Nobel Committee later called the method one of the most important methodological advances in biomedicine of the 1970s, and a route to precise diagnosis and treatment of disease.

Laboratory method (Nature 1975): fusion of antibody-producing cells with tumour cells gives continuous cultures of fused cells secreting antibody of predefined specificity. The Nobel Committee (1984) states that the method allows unlimited production of monoclonal antibodies with predetermined specificity and opens new fields of research and precise diagnosis and treatment of disease. Köhler and Milstein shared the 1984 Nobel Prize in Physiology or Medicine with Niels Jerne.

1975 · Treatment · Hodgkin lymphoma

ABVD versus MOPP: preliminary randomised results (Bonadonna)

In 1975 Bonadonna and colleagues reported early results from a study in which people with advanced Hodgkin disease were randomly given either MOPP or a new four-drug combination, ABVD. About three in four of the people evaluated in each group reached complete remission, and switching to the other regimen after a failure showed no sign of cross-resistance.

Preliminary report of a controlled study randomising ABVD (six cycles) versus MOPP in advanced Hodgkin's disease: 60 patients entered, 45 evaluable for remission induction (MOPP 25, ABVD 20). Complete remission 76% with MOPP and 75% with ABVD, with no difference by stage, histologic type or prior irradiation. Crossover for progression or relapse showed no cross-resistance. The authors note that the lack of long-term follow-up limits comparison.

c. 1975 · Treatment · Melanoma

Dacarbazine: the reference single agent in metastatic melanoma

Dacarbazine, a chemotherapy drug, had its US application approved in 1975, and a later review reports it was approved for metastatic melanoma in the 1970s. For decades it was the reference treatment. Randomised trials of a four-drug regimen and of temozolomide did not show a survival advantage over it. It later served as the control arm of several trials.

Dacarbazine: FDA NDA 017575 original approval 27 May 1975 (Drugs@FDA; indication not listed there). Dartmouth regimen vs dacarbazine (n=240): no survival difference; response 18.5% vs 10.2% (P=0.09). Temozolomide vs dacarbazine (n=305): median OS 7.7 vs 6.4 months; median PFS 1.9 vs 1.5 months (P=0.012).

1975 · Understanding · Multiple myeloma

Durie-Salmon clinical staging system (1975)

In 1975 Durie and Salmon described a staging system for multiple myeloma built on an estimate of how many myeloma cells a person carried. It combined the extent of bone damage, haemoglobin, calcium and the level of abnormal antibody protein in blood and urine, and it tracked with response to treatment and survival.

In 71 patients, myeloma cell mass, calculated from monoclonal immunoglobulin synthesis and metabolism, was predicted by the extent of bone lesions, haemoglobin, serum calcium and serum and urine M-component. Cell mass correlated significantly with response to chemotherapy and survival. The authors synthesised the results into a clinical staging system with three tumour cell mass levels.

1975 · Treatment · Testicular germ cell tumors

Bleomycin combinations for testicular cancer (1975)

Two 1975 reports described bleomycin combined with other drugs in advanced germ-cell tumours of the testis. In one series, 53 of 70 patients with stage III disease responded, and patients with a complete response lived longer than the others. The other, with continuous-infusion bleomycin and vinblastine, reported complete responses in 9 of 23 patients.

Two uncontrolled series. Samuels (Cancer): 83 patients with stage II or III testicular and 7 with extragonadal primaries, bleomycin with vinblastine or a five-drug programme; of 70 stage III, 53 responded (75%): 22 complete, 31 partial; mean survival of complete responders 100+ weeks (3 deaths). Samuels (Cancer Chemother Rep): 23 stage III patients, continuous-infusion bleomycin plus vinblastine; 17 responses, 9 complete (39%); one death from bleomycin pneumonitis.